Sample records for encodes guidance molecules

Guidancemolecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidancemolecule families and their corresponding receptors are described, including the semaphorins/neuropilins/plexins, ephrins and Eph receptors, netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to target these molecules as a therapeutic approach in cancer is discussed. PMID:20139699

In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at 45.degree. C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

Repulsive guidancemolecules (RGMs) are found in vertebrates and chordates and are involved in embryonic development and iron homeostasis. Members of this family are GPI-linked membrane proteins that contain an N-terminal signal peptide, a C-terminal propeptide, and a conserved RGD motif. Vertebrates are known to possess three paralogues; RGMA and RGMB (sometimes called Dragon) are expressed in the nervous system and are thought to play various roles in neural development. Hemojuvelin (HJV; also called repulsive guidancemolecule c, RGMC) is the third member of this family, and mutations in this gene result in a form of juvenile hemochromatosis (type 2A). Phylogenetic analyses of 55 different RGM family sequences from 21 different species support the existence of a novel gene, found only in fish, which we have labeled RGMD. The pattern of conserved residues in each family identifies new candidates for important functional roles, including ligand binding. PMID:17593421

Topographic maps are a two-dimensional representation of one neural structure within another and serve as the main strategy to organize sensory information. The retina’s projection via axons of retinal ganglion cells to midbrain visual centers, the optic tectum/superior colliculus, is the leading model to elucidate mechanisms of topographic map formation. Each axis of the retina is mapped independently using different mechanisms and sets of axon guidancemolecules expressed in gradients to achieve the goal of representing a point in the retina onto a point within the target. An axon’s termination along the temporal-nasal mapping axis is determined by opposing gradients of EphAs and ephrin-As that act through their forward and reverse signaling, respectively, within the projecting axons, each of which inhibits interstitial branching, cooperating with a branch-promoting activity, to generate topographic specific branching along the shaft of the parent axons that overshoot their correct termination zone along the anterior-posterior axis of the target. The dorsal-ventral termination position is then determined using a gradient of ephrin-B that can act as a repellent or attractant depending on the ephrin-B concentration relative to EphB levels on the interstitial branches to guide them along the medial-lateral axis of the target to their correct termination zone, where they arborize. In both cases, axon-axon competition results in axon mapping based on relative rather than absolute levels of repellent or attractant activity. The map is subsequently refined through large-scale pruning driven in large part by patterned retinal activity. PMID:20880989

Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidancemolecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidancemolecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidancemolecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl-glycine as biomarkers for oxidative stress exposure decreased, repulsive guidancemolecule A and levodopa rose. Repulsive guidancemolecule A remained unchanged in levodopa naïve patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidancemolecule A rise may inhibit physiologic mechanisms for neuronal survival. PMID:26880022

Slits are large secreted glycoproteins characterized by an unusual tandem of four LRR (leucine-rich repeat) domains in their N-terminal half. Slit proteins were initially described as repulsive guidance cues in neural development, but it has become clear that they have additional important functions, for instance in the vasculature and immune system. Genetic studies have identified two types of cellular receptors for Slits: Robos (Roundabout) and the HS (heparan sulphate) proteoglycan syndecan. The intracellular signalling cascade downstream of Robo activation is slowly being elucidated, but the mechanism of transmembrane signalling by Robo has remained obscure. No active signalling role for syndecan has yet been demonstrated. Slit-HS interactions may be important for shaping the presumed Slit gradient or presenting Slit at its target cell surface. Recent studies have mapped the binding sites for Robos and HS/heparin to discrete Slit domains. Robos bind to the second LRR domain of Slit, whereas HS/heparin binds with very high affinity to the C-terminal portion of Slit. Slit activity is likely to be modulated by physiological proteolytic cleavage in the region separating the Robo and HS/heparin-binding sites. PMID:16709176

Administration of drugs of abuse induces strong molecular adaptations and plasticity within the mesolimbic dopamine (DA) system, a pathway essential for reward-seeking behavior. Little is known about the specific targets involved in this neuroadaptation process, but there are indications that cocaine and other drugs of abuse share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. Axon guidancemolecules, the very molecular cues that regulate the formation of axon-target connections during development, may mediate these alterations. To test this hypothesis, we investigated mRNA expression changes of 39 axon guidancemolecules, including 17 Semaphorins, 12 Ephs, 8 Ephrins, and 2 neuropilins in the mesolimbic dopamine system of cocaine-treated animals under different paradigms by mean of DNA-Microarray and quantitative real-time PCR. In all cases, strong changes in gene expression are observed, yielding to up or downregulation of these axon guidancemolecules. Our data suggest that cocaine treatment induces activation of a complex program of synaptic rearrangements, which may partly recapitulate the plastic changes occurring during development, and may underlie the important neuroplastic adaptations that occur in the reward- and memory-related brain centers following drug action. We conclude that in some brain regions, exposure to psychomotor-stimulant drugs produce expression changes in axon guidancemolecules, which may contribute to cognitive deficits associated with drug abuse. PMID:15691709

During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidancemolecules, a new family of directional guidance cues. PMID:16939972

Repulsive guidancemolecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways. PMID:23744777

Repulsive guidancemolecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates. Levels of soluble RGMa in the cerebrospinal fluid were decreased in progressive MS patients successfully treated with intrathecal corticosteroid triamcinolone acetonide (TCA), showing functional improvements. In vitro, RGMa monoclonal antibodies (mAbs) reversed RGMa-mediated neurite outgrowth inhibition and chemorepulsion. In animal models of CNS damage and MS, RGMa antibody stimulated regeneration and remyelination of damaged nerve fibers, accelerated functional recovery, and protected the retinal nerve fiber layer as measured by clinically relevant optic coherence tomography. These data suggest that targeting RGMa is a promising strategy to improve functional recovery in MS patients. PMID:25801027

We report the identification and molecular characterization of Dtrk, a Drosophila gene encoding a receptor tyrosine kinase highly related to the trk family of mammalian neurotrophin receptors. The product of the Dtrk gene, gp160Dtrk, is dynamically expressed during Drosophila embryogenesis in several areas of the developing nervous system, including neurons and fasciculating axons. gp160Dtrk has structural homology with neural cell adhesion molecules of the immunoglobulin superfamily and promotes cell adhesion in a homophilic, Ca2+ independent manner. More importantly, this adhesion process specifically activates its tyrosine protein kinase activity. These findings suggest that gp160Dtrk represents a new class of neural cell adhesion molecules that may regulate neuronal recognition and axonal guidance during the development of the Drosophila nervous system. Images PMID:1371458

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidancemolecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment. PMID:26029998

Theileria parva, a tick-transmitted protozoan parasite related to Plasmodium spp., causes the disease East Coast fever, an acute and usually fatal lymphoproliferative disorder of cattle in Africa. Previous studies using sera from cattle that have survived infection identified a polymorphic immunodominant molecule (PIM) that is expressed by both the infective sporozoite stage of the parasite and the intracellular schizont. Here we show that mAb specific for the PIM Ag can inhibit sporozoite invasion of lymphocytes in vitro. A cDNA clone encoding the PIM Ag of the T. parva (Muguga) stock was obtained by using these mAb in a novel eukaryotic expression cloning system that allows isolation of cDNA encoding cytoplasmic or surface Ags. To establish the molecular basis of the polymorphism of PIM, the cDNA of the PIM Ag from a buffalo-derived T. parva stock was isolated and its sequence was compared with that of the cattle-derived Muguga PIM. The two cDNAs showed considerable identity in both the 5{prime} and 3{prime} regions, but there was substantial sequence divergence in the central regions. Several types of repeated sequences were identified in the variant regions. In the Muguga form of the molecule, there were five tandem repeats of the tetrapeptide, QPEP, that were shown, by transfection of a deleted version of the PIM gene, not to react with several anti-PIM mAbs. By isolating and sequencing the genomic version of the gene, we identified two small introns in the 3{prime} region of the gene. Finally, we showed that polyclonal rat Abs against recombinant PIM neutralize sporozoite infectivity in vitro, suggesting that the PIM Ag should be evaluated for its capacity to immunize cattle against East Coast Fever.

The simultaneous detection of a large number of different analytes is important in bionanotechnology research and in diagnostic applications. Nanopore sensing is an attractive method in this regard as the approach can be integrated into small, portable device architectures, and there is significant potential for detecting multiple sub-populations in a sample. Here, we show that highly multiplexed sensing of single molecules can be achieved with solid-state nanopores by using digitally encoded DNA nanostructures. Based on the principles of DNA origami, we designed a library of DNA nanostructures in which each member contains a unique barcode; each bit in the barcode is signalled by the presence or absence of multiple DNA dumbbell hairpins. We show that a 3-bit barcode can be assigned with 94% accuracy by electrophoretically driving the DNA structures through a solid-state nanopore. Select members of the library were then functionalized to detect a single, specific antibody through antigen presentation at designed positions on the DNA. This allows us to simultaneously detect four different antibodies of the same isotype at nanomolar concentration levels. PMID:27043197

Haterumalides are halogenated macrolides with strong antitumor properties, making them attractive targets for chemical synthesis. Unfortunately, current synthetic routes to these molecules are inefficient. The potent haterumalide, oocydin A, was previously identified from two plant-associated bacteria through its high bioactivity against plant pathogenic fungi and oomycetes. In this study, we describe oocydin A (ooc) biosynthetic gene clusters identified by genome sequencing, comparative genomics, and chemical analysis in four plant-associated enterobacteria of the Serratia and Dickeya genera. Disruption of the ooc gene cluster abolished oocydin A production and bioactivity against fungi and oomycetes. The ooc gene clusters span between 77 and 80 kb and encode five multimodular polyketide synthase (PKS) proteins, a hydroxymethylglutaryl-CoA synthase cassette and three flavin-dependent tailoring enzymes. The presence of two free-standing acyltransferase proteins classifies the oocydin A gene cluster within the growing family of trans-AT PKSs. The amino acid sequences and organization of the PKS domains are consistent with the chemical predictions and functional peculiarities associated with trans-acyltransferase PKS. Based on extensive in silico analysis of the gene cluster, we propose a biosynthetic model for the production of oocydin A and, by extension, for other members of the haterumalide family of halogenated macrolides exhibiting anti-cancer, anti-fungal, and other interesting biological properties. PMID:23012376

The simultaneous detection of a large number of different analytes is important in bionanotechnology research and in diagnostic applications. Nanopore sensing is an attractive method in this regard as the approach can be integrated into small, portable device architectures, and there is significant potential for detecting multiple sub-populations in a sample. Here, we show that highly multiplexed sensing of single molecules can be achieved with solid-state nanopores by using digitally encoded DNA nanostructures. Based on the principles of DNA origami, we designed a library of DNA nanostructures in which each member contains a unique barcode; each bit in the barcode is signalled by the presence or absence of multiple DNA dumbbell hairpins. We show that a 3-bit barcode can be assigned with 94% accuracy by electrophoretically driving the DNA structures through a solid-state nanopore. Select members of the library were then functionalized to detect a single, specific antibody through antigen presentation at designed positions on the DNA. This allows us to simultaneously detect four different antibodies of the same isotype at nanomolar concentration levels.

In the olfactory epithelium (OE), odorant receptor stimulation generates cAMP signals that function in both odor detection and the regulation of axon guidancemolecule expression. The enzyme that synthesizes cAMP, adenylyl cyclase 3 (AC3), is coexpressed in olfactory sensory neurons (OSNs) with poly-N-acetyllactosamine (PLN) oligosaccharides determined by the glycosyltransferase β3GnT2. The loss of either enzyme results in similar defects in olfactory bulb (OB) innervation and OSN survival, suggesting that glycosylation may be important for AC3 function. We show here that AC3 is extensively modified with N-linked PLN, which is essential for AC3 activity and localization. On Western blots, AC3 from the wild-type OE migrates diffusely as a heavily glycosylated 200 kDa band that interacts with the PLN-binding lectin LEA. AC3 from the β3GnT2−/− OE loses these PLN modifications, migrating instead as a 140 kDa glycoprotein. Furthermore, basal and forskolin-stimulated cAMP production is reduced 80–90% in the β3GnT2−/− OE. Although AC3 traffics normally to null OSN cilia, it is absent from axon projections that aberrantly target the OB. The cAMP-dependent guidance receptor neuropilin-1 is also lost from β3GnT2−/− OSNs and axons, while semaphorin-3A ligand expression is upregulated. In addition, kirrel2, a mosaically expressed adhesion molecule that functions in axon sorting, is absent from β3GnT2−/− OB projections. These results demonstrate that PLN glycans are essential in OSNs for proper AC3 localization and function. We propose that the loss of cAMP-dependent guidance cues is also a critical factor in the severe axon guidance defects observed in β3GnT2−/− mice. PMID:21525298

DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions. This review highlights some of the most significant and recent strategies along with important results. A special focus on the production of high fidelity DEL technologies with the ability to eliminate screening noise and false positives is included: using a DNA junction called the Yoctoreactor, building blocks (BBs) are spatially confined at the center of the junction facilitating both the chemical reaction between BBs and encoding of the synthetic route. A screening method, known as binder trap enrichment, permits DELs to be screened robustly in a homogeneous manner delivering clean data sets and potent hits for even the most challenging targets. PMID:25732963

When the axons of primary sensory neurons project into the embryonic mammalian spinal cord, they bifurcate and extend rostrocaudally before sending collaterals to specific laminae according to neuronal subclass. The specificity of this innervation has been suggested to be the result both of differential sensitivity to chemorepellants expressed in the ventral spinal cord and of the function of Ig-like neural cell adhesion molecules in the dorsal horn. The relationship between these mechanisms has not been addressed. Focussing on the pathfinding of TrkA+ NGF-dependent axons, we demonstrate for the first time that their axons project prematurely into the dorsal horn of both L1 and TAG-1 knockout mice. We show that axons lacking TAG-1, similar to those lacking L1, are insensitive to wild-type ventral spinal cord (VSC)-derived chemorepellants, indicating that adhesion molecule function is required in the axons, and that this loss of response is explained in part by loss of response to Sema3A. We present evidence that TAG-1 affects sensitivity to Sema3A by binding to L1 and modulating the endocytosis of the L1/neuropilin 1 Sema3A receptor complex. However, TAG-1 appears to affect sensitivity to other VSC-derived chemorepellants via an L1-independent mechanism. We suggest that this dependence of chemorepellant sensitivity on the functions of combinations of adhesion molecules is important to ensure that axons project via specific pathways before extending to their final targets. PMID:18550718

A cDNA encoding isopentenyl monophosphate kinase (IPK) from peppermint (Mentha x piperita) has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Accordingly, an isolated DNA sequence (SEQ ID NO:1) is provided which codes for the expression of isopentenyl monophosphate kinase (SEQ ID NO:2), from peppermint (Mentha x piperita). In other aspects, replicable recombinant cloning vehicles are provided which code for isopentenyl monophosphate kinase, or for a base sequence sufficiently complementary to at least a portion of isopentenyl monophosphate kinase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding isopentenyl monophosphate kinase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant isopentenyl monophosphate kinase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant isopentenyl monophosphate kinase may be used to obtain expression or enhanced expression of isopentenyl monophosphate kinase in plants in order to enhance the production of isopentenyl monophosphate kinase, or isoprenoids derived therefrom, or may be otherwise employed for the regulation or expression of isopentenyl monophosphate kinase, or the production of its products.

The recent advances of the evolutionary molecular engineering revealed the effectiveness of bonding strategy for assignment of the phenotype to its genotype, which non-enveloped viruses such as simple bacteriophages adopt. On the other hand, cellular organisms adopt another kind of the strategy, namely the compartmentalzation of both genotype and phenotype molecules in a single compartment enclosed with a cell membrane. The simplest strategy is that adopted by ribozymes in the RNA world. A single molecule carries both genotype and its phenotype. Based on the definition of “virus”-type and “cell”-type of the assignment strategy, we propose a virus-early/cell-late model of the history of life.

The Epstein-Barr virus (EBV) is known as an oncogenic herpesvirus that has been implicated in the pathogenesis of various malignancies. EBV-encoded RNAs (EBERs) are non-coding RNAs expressed abundantly in latently EBV-infected cells. Herein, I summarize the current understanding of the functions of EBERs, including the interactions with cellular factors through which EBERs contribute to EBV-mediated pathogenesis. Previous studies have demonstrated that EBERs are responsible for malignant phenotypes in lymphoid cells, and can induce several cytokines that can promote the growth of various EBV-infected cancer cells. EBERs were also found to bind retinoic acid-inducible gene I (RIG-I) and thus activate its downstream signaling. Furthermore, EBERs induce interleukin-10, an autocrine growth factor for Burkitt's lymphoma cells, by activating RIG-I/interferon regulatory factor 3 pathway, suggesting that EBER-mediated innate immune signaling modulation contributes to EBV-mediated oncogenesis. Recently, EBV-infected cells were reported to secret EBERs, which were then recognized by toll-like receptor 3 (TLR3), leading to the induction of type I interferon and inflammatory cytokines, and subsequent immune activation. Furthermore, EBER1 was detected in the sera of patients with active EBV-infectious diseases, suggesting that EBER1-meidated TLR3 signaling activation could account for the pathogenesis of active EBV-infectious diseases. PMID:25101570

Semaphorin3A (SEMA3A), an axon guidancemolecule in the nervous system, plays an inhibitory role in oncogenesis. Here, we investigated the expression pattern and biological roles of SEMA3A in head and neck squamous cell carcinoma (HNSCC) by gain-of-function assays using adenovirus transfection and recombinant human SEMA3A protein. In addition, we explored the therapeutic efficacy of SEMA3A against HNSCC in vivo. We found that lower expression of SEMA3A correlated with shorter overall survival and had independent prognostic importance in patients with HNSCC. Both genetic and recombinant SEMA3A protein inhibited cell proliferation and colony formation and induced apoptosis, accompanied by decreased cyclin E, cyclin D, CDK2, CDK4 and CDK6 and increased P21, P27, activated caspase-5 and caspase-7. Moreover, over-expression of SEMA3A suppressed migration, invasion and epithelial-to-mesenchymal transition due in part to the inhibition of NF-κB and SNAI2 in HNSCC cell lines. Furthermore, intratumoral SEMA3A delivery significantly stagnated tumor growth in a xenograft model. Taken together, our results indicate that SEMA3A serves as a tumor suppressor during HNSCC tumorigenesis and a new target for the treatment of HNSCC. PMID:26755661

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidancemolecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein-ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein-DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs. PMID:27119259

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 SNPs in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in HWE in controls (P<0.01). 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNFA/LTA region . Genotype phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r2=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria [P=0.007, OR=0.78 (95% CI; 0.65-0.93)] and death [P=0.028, OR=0.58 (95% CI; 0.37-0.93)] than those with AA and AG genotypes. In summary, variants in 6 genes encoding adhesion and pro-inflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings. PMID:22673309

Abstract Oncolytic viruses have shown promise as gene delivery vehicles in the treatment of cancer; however, their efficacy may be inhibited by the induction of anti-viral antibody titers. Fowlpox virus is a nonreplicating and nononcolytic vector that has been associated with lesser humoral but greater cell-mediated immunity in animal tumor models. To test whether fowlpox virus gene therapy is safe and can elicit immune responses in patients with cancer, we conducted a randomized phase I clinical trial of two recombinant fowlpox viruses encoding human B7.1 or a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3; TRICOM). Twelve patients (10 with melanoma and 2 with colon adenocarcinoma) enrolled in the trial and were randomized to rF-B7.1 or rF-TRICOM administered in a dose escalation manner (∼3.7×107 or ∼3.7×108 plaque-forming units) by intralesional injection every 4 weeks. The therapy was well tolerated, with only four patients experiencing grade 1 fever or injection site pain, and there were no serious adverse events. All patients developed anti-viral antibody titers after vector delivery, and posttreatment anti-carcinoembryonic antigen antibody titers were detected in the two patients with colon cancer. All patients developed CD8+ T cell responses against fowlpox virus, but few responses against defined tumor-associated antigens were observed. This is the first clinical trial of direct (intratumoral) gene therapy with a nononcolytic fowlpox virus. Treatment was well tolerated in patients with metastatic cancer; all subjects exhibited anti-viral antibody responses, but limited tumor-specific T cell responses were detected. Nononcolytic fowlpox viruses are safe and induce limited T cell responses in patients with cancer. Further development may include prime–boost strategies using oncolytic viruses for initial priming. PMID:24484178

This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID:20300212

The authors have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of the Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-[gamma]/[delta] dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains. 48 refs., 6 figs., 2 tabs.

LFA-1, an antigen involved in cytolytic T lymphocyte-mediated killing, and Mac-1, the receptor for complement component C3bi, constitute a family of structurally and functionally related cell surface glycoproteins involved in cellular interactions. In both mouse and man, Mac-1 (OKM1) and LFA-1 share a common 95-kDa ..beta.. subunit but are distinguished by their ..cap alpha.. chains, which have different cellular distributions, apparent molecular masses (165 and 177 kDa, respectively), and peptide maps. The authors report the isolation of a genomic clone from a human genomic library that on transfection into mouse fibroblasts produced a molecule(s) reactive with monoclonal antibodies to OKM1, to LFA-1, and to platelet glycoprotein IIb-IIIa. This gene was cloned by several cycles of transfection of L cells with a human genomic library cloned in lambda phase Charon 4A and subsequent rescue of the lambda phage. Transfection with the purified recombinant lambda DNA yielded a transfectant that expressed the three human ..cap alpha.. chains of OKM1, LFA-1, and glycoprotein IIb-IIIa, presumably in association with the murine ..beta.. chain.

Herpes simplex virus 1 (HSV-1) causes herpes stromal keratitis (HSK), a sight-threatening disease of the cornea for which no vaccine exists. A replication-defective, HSV-1 prototype vaccine bearing deletions in the genes encoding ICP8 and the virion host shutoff (vhs) protein reduces HSV-1 replication and disease in a mouse model of HSK. Here we demonstrate that combining deletion of ICP8 and vhs with virus-based expression of B7 costimulation molecules created a vaccine strain that enhanced T cell responses to HSV-1 compared with the ICP8−vhs− parental strain, and reduced the incidence of keratitis and acute infection of the nervous system after corneal challenge. Post-challenge T cell infiltration of the trigeminal ganglia and antigen-specific recall responses in local lymph nodes correlated with protection. Thus, B7 costimulation molecules expressed from the genome of a replication-defective, ICP8−vhs− virus enhance vaccine efficacy by further reducing HSK. PMID:21826207

The human TAX-1 gene (HGMW-approved symbol TAX1) is located on chromosome 1 (1q32.1) and encodes the neuronal cell adhesion molecule TAG-1/axonin-1. The gene product, termed TAG-1 in the rat and axonin-1 in the chicken, is composed of six immunoglobulin (Ig)-like and four fibronectin type III (FNIII)-like domains. It is found predominantly on the axons of particular nerve fiber tracts during neural development, and it has been demonstrated to function as a potent substratum for neurite outgrowth in vitro. Here we report the cloning and structural characterization of the TAX-1 gene. The transcribed region of the TAX-1 gene extends over about 40 kb. Like its chicken homologue, the human TAX-1 gene consists of 23 exons. Two GT/CA microsatellites were localized in the first intron; a polymorphism was found for one of them. Reporter gene analysis with serially truncated fragments of the 5{prime}-flanking region indicated that a 164-bp fragment located immediately upstream of the putative transcription initiation site was sufficient to function as a basal promoter. 45 refs., 3 figs., 2 tabs.

Carboxypeptidase A6 (CPA6) is an extracellular matrix metallocarboxypeptidase that modulates peptide and protein function by removal of hydrophobic C-terminal amino acids. Mutations in the human CPA6 gene that reduce enzymatic activity in the extracellular matrix are associated with febrile seizures, temporal lobe epilepsy, and juvenile myoclonic epilepsy. The characterization of these human mutations suggests a dominant mode of inheritance by haploinsufficiency through loss of function mutations, however the total number of humans with pathologic mutations in CPA6 identified to date remains small. To better understand the relationship between CPA6 and seizures we investigated the effects of morpholino knockdown of cpa6 mRNA in zebrafish (Danio rerio) larvae. Knockdown of cpa6 mRNA resulted in resistance to the effect of seizure-inducing drugs pentylenetetrazole and pilocarpine on swimming behaviors. Knockdown of cpa6 mRNA also reduced the levels of mRNAs encoding neuropeptide precursors (bdnf, npy, chga, pcsk1nl, tac1, nts, edn1), a neuropeptide processing enzyme (cpe), transcription factor (c-fos), and molecules implicated in glutamatergic signaling (grin1a and slc1a2b). Treatment of zebrafish embryos with 60 mM pilocarpine for 1 hour led to reductions in levels of many of the same mRNAs when measured 1 day after pilocarpine exposure, except for c-fos which was elevated 1 day after pilocarpine treatment. Pilocarpine treatment, like cpa6 knockdown, led to a reduced sensitivity to pentylenetetrazole when tested 1 day after pilocarpine treatment. Taken together, these results add to mounting evidence that peptidergic systems participate in the biological effects of seizure-inducing drugs, and are the first in vivo demonstration of the molecular and behavioral consequences of cpa6 insufficiency. PMID:27050163

Carboxypeptidase A6 (CPA6) is an extracellular matrix metallocarboxypeptidase that modulates peptide and protein function by removal of hydrophobic C-terminal amino acids. Mutations in the human CPA6 gene that reduce enzymatic activity in the extracellular matrix are associated with febrile seizures, temporal lobe epilepsy, and juvenile myoclonic epilepsy. The characterization of these human mutations suggests a dominant mode of inheritance by haploinsufficiency through loss of function mutations, however the total number of humans with pathologic mutations in CPA6 identified to date remains small. To better understand the relationship between CPA6 and seizures we investigated the effects of morpholino knockdown of cpa6 mRNA in zebrafish (Danio rerio) larvae. Knockdown of cpa6 mRNA resulted in resistance to the effect of seizure-inducing drugs pentylenetetrazole and pilocarpine on swimming behaviors. Knockdown of cpa6 mRNA also reduced the levels of mRNAs encoding neuropeptide precursors (bdnf, npy, chga, pcsk1nl, tac1, nts, edn1), a neuropeptide processing enzyme (cpe), transcription factor (c-fos), and molecules implicated in glutamatergic signaling (grin1a and slc1a2b). Treatment of zebrafish embryos with 60 mM pilocarpine for 1 hour led to reductions in levels of many of the same mRNAs when measured 1 day after pilocarpine exposure, except for c-fos which was elevated 1 day after pilocarpine treatment. Pilocarpine treatment, like cpa6 knockdown, led to a reduced sensitivity to pentylenetetrazole when tested 1 day after pilocarpine treatment. Taken together, these results add to mounting evidence that peptidergic systems participate in the biological effects of seizure-inducing drugs, and are the first in vivo demonstration of the molecular and behavioral consequences of cpa6 insufficiency. PMID:27050163

In this column, the author shares and comments on early childhood educators' use of guidance to foster young children's development and learning. He defines guidance as the commitment a teacher makes to teaching children how to solve their problems, rather than punishing them for having problems they haven't yet learned how to solve. The focus of…

States that children need proper guidance and boundaries to reap the benefits of the Internet. Focuses on two issues: how parents can protect their children from the Internet's potential dangers and how they can help their children use the Internet to get work done. Includes suggestions for teachers to help parents meet these challenges. (VWC)

The 16,937-nuceotide sequence of the linear mitochondrial DNA (mt-DNA) molecule of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa) - the first mtDNA sequence from the class Scypozoa and the first sequence of a linear mtDNA from Metazoa - has been determined. This sequence contains genes for 13 energy pathway proteins, small and large subunit rRNAs, and methionine and tryptophan tRNAs. In addition, two open reading frames of 324 and 969 base pairs in length have been found. The deduced amino-acid sequence of one of them, ORF969, displays extensive sequence similarity with the polymerase [but not the exonuclease] domain of family B DNA polymerases, and this ORF has been tentatively identified as dnab. This is the first report of dnab in animal mtDNA. The genes in A. aurita mtDNA are arranged in two clusters with opposite transcriptional polarities; transcription proceeding toward the ends of the molecule. The determined sequences at the ends of the molecule are nearly identical but inverted and lack any obvious potential secondary structures or telomere-like repeat elements. The acquisition of mitochondrial genomic data for the second class of Cnidaria allows us to reconstruct characteristic features of mitochondrial evolution in this animal phylum. PMID:16945488

To identify novel antivirals to the hepatitis C virus (HCV) NS4B protein, we utilized encoded library technology (ELT), which enables purified proteins not amenable to standard biochemical screening methods to be tested against large combinatorial libraries in a short period of time. We tested NS4B against several DNA-encoded combinatorial libraries (DEL) and identified a single DEL feature that was subsequently progressed to off-DNA synthesis. The most active of the initial synthesized compounds had 50% inhibitory concentrations (IC50s) of 50 to 130 nM in a NS4B radioligand binding assay and 300 to 500 nM in an HCV replicon assay. Chemical optimization yielded compounds with potencies as low as 20 nM in an HCV genotype 1b replicon assay, 500 nM against genotype 1a, and 5 μM against genotype 2a. Through testing against other genotypes and genotype 2a-1b chimeric replicons and from resistance passage using the genotype 1b replicon, we confirmed that these compounds were acting on the proposed first transmembrane region of NS4B. A single sequence change (F98L) was identified as responsible for resistance, and it was thought to largely explain the relative lack of potency of this series against genotype 2a. Unlike other published series that appear to interact with this region, we did not observe sensitivity to amino acid substitutions at positions 94 and 105. The discovery of this novel compound series highlights ELT as a valuable approach for identifying direct-acting antivirals to nonenzymatic targets. PMID:25824229

Describes problems in devising a Text Encoding Initiative (TEI) encoding format for dictionaries. Asserts that the high degree of structuring and compression of information are among the most complex text types treated in the TEI. Concludes that the source of some TEI problems lies in the design of Standard Generalized Markup Language (SGML). (CFR)

Mycobacterium tuberculosis (Mtb), the sole cause of Tuberculosis (TB), is still a major global problem. The discovery of new anti-tubercular drugs is needed to face the increasing TB cases, especially to prevent the increase of cases with resistant Mtb. A potential novel drug target is the Mtb PhoR sensor domain protein which is the histidine kinase extracellular domain for receiving environmental signals. This protein is the initial part of the two-component system PhoR-PhoP regulating 114 genes related to the virulence of Mtb. In this study, the gene encoding PhoR sensor domain (SensPhoR) was subcloned from pGEM-T SensPhoR from the previous study (Suwanto, 2012) to pColdII. The construct pColdII SensPhoR was confirmed through restriction analysis and sequencing. Using the construct, SensPhoR was overexpressed at 15°C using Escherichia coli BL21 (DE3). Low temperature was chosen because according to the solubility prediction program of recombinant proteins from The University of Oklahama, the PhoR sensor domain has a chance of 79.8% to be expressed as insoluble proteins in Escherichia coli's (E. coli) cytoplasm. This prediction is also supported by other similar programs: PROSO and PROSO II. The SDS PAGE result indicated that the PhoR sensor domain recombinant protein was overexpressed. For future studies, this protein will be purified and used for structure analysis which can be used to find potential drugs through rational drug design.

The ENCODE project represents a major leap from merely describing and comparing genomic sequences to surveying them for direct indicators of function. The astounding quantity of data produced by the ENCODE consortium can serve as a map to locate specific landmarks, guide hypothesis generation, and lead us to principles and mechanisms underlying genome biology. Despite its broad appeal, the size and complexity of the repository can be intimidating to prospective users. We present here some background about the ENCODE data, survey the resources available for accessing them, and describe a few simple principles to help prospective users choose the data type(s) that best suit their needs, where to get them, and how to use them to their best advantage. PMID:26962025

This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous. 13 figs.

This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous.

Blood vessels and nervous fibers grow in parallel, for they express similar receptors for chemokine substances. Recently, much attention is being given to studying guidance receptors and their ligands besides the growth factors, cytokines, and chemokines necessary to form structures in the nervous and vascular systems. Such guidancemolecules determine trajectory for growing axons and vessels. Guidancemolecules include Ephrins and their receptors, Neuropilins and Plexins as receptors for Semaphorins, Robos as receptors for Slit-proteins, and UNC5B receptors binding Netrins. Apart from these receptors and their ligands, urokinase and its receptor (uPAR) and T-cadherin are also classified as guidancemolecules. The urokinase system mediates local proteolysis at the leading edge of cells, thereby providing directed migration. T-cadherin is a repellent molecule that regulates the direction of growing axons and blood vessels. Guidance receptors also play an important role in the diseases of the nervous and cardiovascular systems. PMID:26567567

This bibliography lists articles and books dealing with elementary school guidance. The bibliography is arranged alphabetically by author. No annotations are given. Approximately 70 titles are given, covering most phases of elementary guidance. (KJ)

An isolated and purified DNA moleculeencoding a DNA repair protein, p95, is provided, as is isolated and purified p95. Also provided are methods of detecting p95 and DNA encoding p95. The invention further provides p95 knock-out mice.

A complete revision of the orbiter powered flight guidance scheme is presented. A unified approach to powered flight guidance was taken to accommodate all phases of exo-atmospheric orbiter powered flight, from ascent through deorbit. The guidance scheme was changed from the previous modified version of the Lambert Aim Point Maneuver Mode used in Apollo to one that employs linear tangent guidance concepts. This document replaces the previous ascent phase equation document.

A two-part study was conducted to evaluate modern flight deck automation and interfaces. In the first part, a survey was performed to validate the existence of automation surprises with current pilots. Results indicated that pilots were often surprised by the behavior of the automation. There were several surprises that were reported more frequently than others. An experimental study was then performed to evaluate (1) the reduction of automation surprises through training specifically for the vertical guidance logic, and (2) a new display that describes the flight guidance in terms of aircraft behaviors instead of control modes. The study was performed in a simulator that was used to run a complete flight with actual airline pilots. Three groups were used to evaluate the guidance display and training. In the training, condition, participants went through a training program for vertical guidance before flying the simulation. In the display condition, participants ran through the same training program and then flew the experimental scenario with the new Guidance-Flight Mode Annunciator (G-FMA). Results showed improved pilot performance when given training specifically for the vertical guidance logic and greater improvements when given the training and the new G-FMA. Using actual behavior of the avionics to design pilot training and FMA is feasible, and when the automated vertical guidance mode of the Flight Management System is engaged, the display of the guidance mode and targets yields improved pilot performance.

This report discusses one of the consistent problems in school counseling and guidance-that of furnishing concrete evidence concerning the effects of counseling and guidance activities on the development of children. The following causal factors are discussed: (1) the difficulty of pinning down abstractly stated goals in an operational manner at…

At the request of the Department of Energy`s (DOE) Information Management (IM) Council, IM representatives from nearly all Headquarters (HQ) organizations have been meeting over the past year as the Corporate Guidance Group (CGG) to develop useful and sound corporate information management (IM) guidance. The ability of the Department`s IM community to develop such unified guidance continues to be critical to the success of future Departmental IM planning processes and the establishment of a well-coordinated IM environment between Headquarters and field organizations. This report, with 26 specific corporate IM guidance items documented and unanimously agreed to, as well as 12 items recommended for further development and 3 items deferred for future consideration, represents a highly successful effort by the IM community. The effort has proven that the diverse DOE organizations can put aside individual preferences and work together towards a common and mutually beneficial goal. In examining most areas and issues associated with information management in the Department, they have developed specific, far-reaching, and useful guidance. The IM representatives recommend that the documented guidance items provided in this report and approved by the DOE IM Council be followed by all IM organizations. The representatives also strongly recommend that the guidance process developed by the CGG be the single process for developing corporate IM guidance.

This paper contains results from ascent guidance studies conducted at the NASA Marshall Space Flight Center. The studies include investigation of different guidance schemes for a variety of potential launch vehicles. Criteria of a successful ascent guidance scheme are low operations cost, satisfaction of load indicator constraints, and maximization of performance. Results show that open-loop designs as a function of altitude or velocity are preferable to designs that are functions of time. Optimized open-loop trajectories can increase performance while maintaining load indicators within limits. Closed-loop atmospheric schemes that involve linear tangent steering or feedback of velocity terms for trajectory modification did not yield any improvement. Early release of vacuum closed-loop guidance, including use during solid rocket booster operation, yields some improvements. Evaluation of a closed-loop optimization scheme for flying through the atmosphere shows no advantages over open-loop optimization. Dispersion study results for several potential guidance schemes and launch vehicles are included in the paper and are not a discriminator between guidance schemes. The primary cost driver is mission operations philosophy, not choice of guidance scheme. More autonomous guidance schemes can help in movement towards a philosophy that would reduce operations costs.

Elementary guidance, deriving much of its content from the developmental phenomena of middle childhood, is viewed as the maximization of human potentiality in the total range of the population. Included in the list of elementary school guidance objectives are (1) aiding academic development, (2) helping children develop health self-concepts, (3)…

The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

This paper describes the design of the entry guidance for the Space Shuttle Orbiter. This guidance provides the steering commands for trajectory control from initial penetration of the earth's atmosphere until the terminal area guidance is activated at an earth-relative speed of 2500 fps. At this point, the Orbiter is at a distance of about 50 nmi from the runway threshold, and at an altitude of about 80,000 ft. The entry guidance design is based on an analytic solution of the equations of motion defining the drag acceleration profile that meets the terminal criteria of the entry flight while maintaining the flight within systems and operational constraints. Guidance commands, which are based on a control law that ensures damping of oscillatory type trajectory motion, are computed to steer the Orbiter to this drag acceleration profile.

Laser driving gun missile guidance type beam of laser information field formed by any link failure or reduced stability will directly lead to ballistic or miss out of control, and based on this, this paper designed the driving beam of laser guided missile guidance beam type forming device modulation and zoom mechanism, in order to make the missile can recognize its position in the laser beam, laser beam gun missile, by means of spatial encoding of the laser beam laser beam into information after forming device, a surface to achieve the purpose of precision guidance.

We report the vibrational signatures of a single H2O molecule occupying distinct sites of the hydration network in the Cs(+)(H2O)6 cluster. This is accomplished using isotopomer-selective IR-IR hole-burning on the Cs(+)(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs(+)(D2O)6 ion. The OH stretching pattern of the Cs(+)(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structural information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs(+)(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs(+)(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy. With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions. PMID:26896984

We report the vibrational signatures of a single H2O molecule occupying distinct sites of the hydration network in the Cs+(H2O)6 cluster. This is accomplished using isotopomer-selective IR-IR hole-burning on the Cs+(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs+(D2O)6 ion. The OH stretching pattern of the Cs+(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structural information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs+(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs+(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy. With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions.

The NeoGenesis Automated Ligand Identification System (ALIS), an affinity selection-mass spectrometry (AS-MS) process consisting of a rapid size-exclusion chromatography stage integrated with reverse-phase chromatography, electrospray mass spectrometry, and novel data searching algorithms, was used to screen mass-encoded, 2500-member combinatorial libraries, leading to the discovery of a novel, bioactive ligand for the anti-infective target Escherichia coli dihydrofolate reductase (DHFR). Synthesis of the mass-encoded, ligand-containing library, discussion of the deconvolution process for verifying the structure of the ligand through independent synthesis and screening in a small mixture (sub-library) format, and ALIS-MS/MS techniques to assign its regioisomeric connectivity are presented. ALIS-based competition experiments between the newly discovered ligand and other, known DHFR ligands, and biological activity assessments with stereo- and regioisomers of the hit compound confirm its DHFR-specific biological activity. The method described requires no foreknowledge of the structure or biochemistry of the protein target, consumes less than 1 [mu]g protein to screen >2500 compounds in a single experiment, and enables screening of >250,000 compounds per system per day. These advantages highlight the potential of the ALIS method for drug discovery against genomic targets with unknown biological function, as well as validated targets for which traditional discovery efforts have failed.

This monograph describes how the comprehensive guidance model is transforming elementary-secondary school guidance and counseling programs in schools across the country. It incorporates the ideas and experiences of 12 guidance program developers in the actual use of the comprehensive guidance model in diverse school and cultural settings. The book…

Explores the conflict in guidance arising from the desire to consider the needs of society while guaranteeing individual freedom of choice. Discusses the theoretical basis of vocational guidance. Gives examples of "domestication" and "transformation" approaches to guidance and discusses the consequences of viewing guidance as a change strategy.(KO)

The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments. PMID:26527727

The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments. PMID:26527727

Our previous work reported that most Enterococcus faecalis strains adhered to the extracellular matrix proteins collagen types I and IV and laminin after growth at 46 degrees C, but not 37 degrees C, and we subsequently identified an E. faecalis sequence, ace, that encodes a bacterial adhesin similar to the collagen binding protein Cna of Staphylococcus aureus. In this study, we examined the diversity of E. faecalis-specific ace gene sequences among different isolates obtained from various geographic regions as well as from various clinical sources. A comparison of nucleotide and deduced amino acid sequences of Ace from nine E. faecalis strains identified a highly conserved N-terminal A domain, followed by a variable B domain which contains two to five repeats of 47 amino acids in tandem array, preceded by a 20-amino-acid partial repeat. Using 17 other strains collected worldwide, the 5' region of ace that encodes the A domain was sequenced, and these sequences showed > or =97.5% identity. Among the previously reported five amino acids critical for collagen binding by Cna of S. aureus, four were found to be identical in Ace from all strains tested. Polyclonal immune rabbit serum prepared against recombinant Ace A derived from E. faecalis strain OG1RF detected Ace in mutanolysin extracts of seven of nine E. faecalis strains after growth at 46 degrees C; Ace was detected in four different molecular sizes that correspond to the variation in the B repeat region. To determine if there was any evidence to indicate that Ace might be produced under physiological conditions, we quantitatively assayed sera collected from patients with enterococcal infections for the presence of anti-Ace A antibodies. Ninety percent of sera (19 of 21) from patients with E. faecalis endocarditis showed reactivity with titers from 1:32 to >1:1,024; the only 2 sera which lacked antibodies to Ace A had considerably lower titers of antibodies to other E. faecalis antigens as well. Human

The long-term goal of this research is to identify the signaling molecules that mediate plant cell-cell interactions during pollination. The immediate goals of this project are to perform genetic and molecular analysis of pollen tube guidance. Specifically, we proposed to: 1. Characterize the pistil components that direct pollen tube navigation using the Arabidopsis thaliana in vitro pollen tube guidance system 2. Identify pistil signals that direct pollen tube guidance by a) using microarrays to profile gene expression in developing pistils, and b) employing proteomics and metabolomics to isolate pollen tube guidance signals. 3. Explore the genetic basis of natural variation in guidance signals, comparing the in vitro interactions between pollen and pistils from A. thaliana and its close relatives.

Genetically encoded sensors allow real-time monitoring of biological molecules at a subcellular resolution. A tremendous variety of such sensors for biological molecules became available in the past 15 years, some of which became indispensable tools that are used routinely in many laboratories. One of the exciting applications of genetically encoded sensors is the use of these sensors in investigating cellular transport processes. Properties of transporters such as kinetics and substrate specificities can be investigated at a cellular level, providing possibilities for cell-type specific analyses of transport activities. In this article, we will demonstrate how transporter dynamics can be observed using genetically encoded glutamine sensor as an example. Experimental design, technical details of the experimental settings, and considerations for post-experimental analyses will be discussed. PMID:25146898

Although the function and effects of many growth factors and extracellular matrix (ECM) molecules have been described for several periodontal tissues in vivo and in vitro, the molecular interactions involved in the communication between cells of the periodontal ligament and the alveolar bone are poorly understood. To contribute to the identification of such interactions, we have generated co-cultures (CCs) of periodontal ligament fibroblasts (PDLs) and alveolar bone cells (ABCs) and compared mRNA expression for various growth factors, ECM molecules, and matrix metalloproteinase13 (MMP13) after 1 and 2 weeks with matched mono-cultures (MCs) by reverse transcription/polymerase chain reaction. Compared with CCs of 1 week, PDLs and ABCs after 2 weeks revealed relatively high levels of all analyzed mRNAs, viz., for EGF, HGF, VEGF, TGFbeta1, collagen-I (COL1), osteonectin (ON), fibronectin (FN1), and MMP13. At week 2, when compared with MCs, CCs showed an elevation of all tested mRNAs in PDLs and ABCs, except for TGFbeta1 and FN1, which only increased in PDLs. After 1 week, when CCs were compared with MCs, mRNAs for HGF and TGFbeta1 were less abundant in PDLs and ABCs, whereas the other genes exhibited lower expression levels in only one of the cell types. Analysis of our data indicated that the expression of mRNAs for growth factors and for COL1, ON, FN1, and MMP13 was modulated in the distinct cell types with respect to culture time and culture type. The differences in the mRNA expression patterns between CCs and MCs suggest that the respective genes are involved in the molecular interactions of PDLs and ABCs. PMID:15668800

Materials contained in this career guidance unit are designed to enable senior high school students to relate their abilities scores from the Developed Abilities Performance (DAP) instrument to actual vocational areas and Long Range [occupational] Goals (LRG) for later indepth study. The length of the unit is six 55-minute periods. Instructional…

The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

To differentiate is to make different, distinct, or specialized (Costello, 1994). Differentiation has become popular in education as an instructional philosophy aimed at equitably meeting the learning needs of all students in the classroom. Differentiated planning and delivery of classroom guidance is also necessary for appropriate school…

Counseling and guidance services are vital in any school curriculum. Counselors may themselves be dealing with students of diverse abilities and handicaps. Counselors may have to work with students affected by drug addiction, fetal alcohol syndrome, homelessness, poverty, Acquired Immune Deficiency Syndrome (AIDS) and divorce. Students may present…

This packet of materials was developed for workshops provided to teams of school counselors and administrators for the purpose of developing knowledge and competencies in the delivery of a comprehensive, sequential, developmental guidance program. Section I contains a rationale, definition, and description of program components. In section II…

This paper examines quality issues in career guidance, counseling, and information services in Europe and elsewhere from a range of different perspectives related to economic, ethical, and/or effectiveness criteria. Selected examples from the European Union member states, Canada, and the United States are used to illustrate how quality is…

The vocational education volume considers questions of career development, the role of guidance in the school, vocational training, the relation of self-concept to vocational choice, and occupational information. Twenty-six papers deal with theories of vocational behavior, the success of vocational education programs, and testing information.…

A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

School administrators and developmental guidance is the topic of the first speech. Developmental guidance, concerned with personalizing the educational experience, should be available to each child to gain self-understanding. Major responsibilities of the elementary guidance department are pupil appraisal, consultation, and developmental…

A panoramic view of Guidance Division general sessions and workshops covering some exemplary career guidance programs, as well as such topics as career choice, leadership, evaluation, and program development and management. Presented at the Guidance division session of the American Vocational Association 1971 annual meeting. (Editor/MU)

Progressive transmission is a method of transmitting and displaying imagery in stages of successively improving quality. The subsampled lowpass image representations generated by a wavelet transformation suit this purpose well, but for best results the order of presentation is critical. Candidate data for transmission are best selected using dynamic prioritization criteria generated from image contents and viewer guidance. We show that wavelets are not only suitable but superior when used to encode data for progressive transmission at non-uniform resolutions. This application does not preclude additional compression using quantization of highpass coefficients, which to the contrary results in superior image approximations at low data rates.

The Space Station will bring a great increase in rendezvous traffic. Formerly, rendezvous has been expensive in terms of time and crew involvement. Multiple trajectory adjustments on separate orbits have been required to meet safety, lighting, and geometry requirements. This paper describes a new guidance technique in which the approach trajectory is shaped by a sequence of velocity increments in order to satisfy multiple constraints within a single orbit. The approach phase is planned before the mission, leaving a group of free parameters that are optimized by onboard guidance. Fuel penalties are typically a few percent, compared to unshaped Hohmann transfers, and total fuel costs can be less than those of more time-consuming ways of meeting the same requirements.

This document describes the background on expanding public participation in the Resource Conservation and Recovery Act and DOE`s response. The bulletin also describes the changes made by the final rule to existing regulations, guidance provided by EPA in the preamble and in the revised RCRA Public Participation Manual, the relationship between public participation and environmental justice, and DOE`s recent public participation and environmental justice initiatives.

In the past 5–10 years, the power of the green fluorescent protein (GFP) and its numerous derivatives has been harnessed toward the development of genetically encoded fluorescent biosensors. These sensors are incorporated into cells or organisms as plasmid DNA, which leads the transcriptional and translational machinery of the cell to express a functional sensor. To date, over 100 different genetically encoded biosensors have been developed for targets as diverse as ions, molecules and enzymes. Such sensors are instrumental in providing a window into the real-time biochemistry of living cells and whole organisms, and are providing unprecedented insight into the inner workings of a cell. PMID:21251723

In the past several years, a great deal has been learnt about the molecular basis through which specific neural pathways in the visual system are established during embryonic development. This review provides a framework for understanding the principles of retinal ganglion cell axon guidance, and introduces some of the families of axon guidancemolecules involved. In addition, the potential relevance of retinal axon guidance to human visual developmental disorders, and to retinal axon regeneration, is discussed. PMID:12714414

Despite the tremendous progress achieved in both vasculogenesis and angiogenesis in the last decade, little is still known about the molecular mechanisms underlying the pathfinding of blood vessels during their formation. However, emerging evidence shows that different axonal guidance cues, including members of the Slit and semaphorin families, are also involved in the blood vessel guidance, suggesting that blood vessels and nerves share common mechanisms in choosing and following specific paths to reach their respective targets. These promising findings open novel avenues not only in vascular biology but also in therapeutic angiogenesis. Indeed, the identification of new molecules involved in the guidance of blood vessels may be helpful in designing angiogenic strategies, which would insure both the formation of new blood vessels and their guidance into an organized and coordinated network. PMID:15664389

We describe a general concept of using the spatial information encoded in the time-dependent polarization of high harmonic radiation generated by orthogonally polarized two-color laser fields. The main properties of recolliding electron wave packets driven by such fields are reviewed. It is shown that in addition to the recollision energy the angle of recollision of such wave packets, which is directly mapped onto the polarization direction of the emitted high harmonic radiation, varies on a sub-laser-cycle time-scale. Thus, a mapping between the polarization angle and the frequency of the emitted radiation is established on an attosecond time scale. While the polarization angle encodes the spatial properties of the recollision process, the frequency is linked to time via the well-known dispersion relations of high harmonic generation. Based on these principles, we show that in combination with polarization selective detection the use of orthogonally polarized drive pulses for high harmonic generation permit one to construct spatially resolved attosecond measurements. Here, we present two examples of possible applications: (i) a method for isolating a single attosecond pulse from an attosecond pulse train which is more efficient than the cut-off selection method, and (ii) a technique for orbital tomography of molecules with attosecond resolution.

The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

Current technologies allow the generation of artificial DNA molecules and/or the ability to alter the DNA sequences of existing DNA molecules. With a careful coding scheme and arrangement, it is possible to encode important information as an artificial DNA strand and store it in a living host safely and permanently. This inventive technology can be used to identify origins and protect R&D investments. It can also be used in environmental research to track generations of organisms and observe the ecological impact of pollutants. Today, there are microorganisms that can survive under extreme conditions. As well, it is advantageous to consider multicellular organisms as hosts for stored information. These living organisms can provide as memory housing and protection for stored data or information. The present invention provides well for data storage in a living organism wherein at least one DNA sequence is encoded to represent data and incorporated into a living organism.

The station-keeping guidance system is described, which is designed to automatically keep one orbiting vehicle within a prescribed zone fixed with respect to another orbiting vehicle. The active vehicle, i.e. the one performing the station-keeping maneuvers, is referred to as the shuttle. The other passive orbiting vehicle is denoted as the workshop. The passive vehicle is assumed to be in a low-eccentricity near-earth orbit. The primary navigation sensor considered is a gimballed tracking radar located on board the shuttle. It provides data on relative range and range rate between the two vehicles. Also measured are the shaft and trunnion axes gimbal angles. An inertial measurement unit (IMU) is provided on board the orbiter. The IMU is used at all times to provide an attitude reference for the vehicle. The IMU accelerometers are used periodically to monitor the velocity-correction burns applied to the shuttle during the station-keeping mode. The guidance system is capable of station-keeping the shuttle in any arbitrary position with respect to the workshop by periodically applying velocity-correction pulses to the shuttle.

The paper describes a method for guiding a dynamic system through a given set of points. The paradigm is a fully automatic aircraft subject to air traffic control (ATC). The ATC provides a sequence of way points through which the aircraft trajectory must pass. The way points typically specify time, position, and velocity. The guidance problem is to synthesize a system state trajectory which satisfies both the ATC and aircraft constraints. Complications arise because the controlled process is multi-dimensional, multi-axis, nonlinear, highly coupled, and the state space is not flat. In addition, there is a multitude of possible operating modes, which may number in the hundreds. Each such mode defines a distinct state space model of the process by specifying the state space coordinatization, the partition of the controls into active controls and configuration controls, and the output map. Furthermore, mode transitions must be smooth. The guidance algorithm is based on the inversion of the pure feedback approximations, which is followed by iterative corrections for the effects of zero dynamics. The paper describes the structure and modules of the algorithm, and the performance is illustrated by several example aircraft maneuvers.

This paper presents a parametric yaw steering law which has been used to provide closed-loop yaw guidance for the launch of the HEAO (High Energy Astronomy Observatory) satellite mission using the Atlas/Centaur launch vehicle. This bilinear tangent steering law provides near optimal yaw steering for maneuvers requiring insertion into orbits with a specified inclination and node. Bilinear tangent steering is shown to be optimal in both the pitch and yaw planes when a uniform gravitational field is assumed. The conditions under which the general bilinear tangent laws degenerate into linear tangent and constant attitude laws are presented. The flight computer implementation of these laws in a rotating coordinate system using real-time integration of the equations of motion is detailed. Explicit solution of the parametric guidance equations requires the inflight solution of (2x2) two-point boundary value problems in the pitch and yaw planes. Excellent results are obtained even for very large (greater than 50 deg) out-of-plane steering angles.

A novel nonlinear missile guidance law against maneuvering targets is designed based on the principles of partial stability. It is demonstrated that in a real approach which is adopted with actual situations, each state of the guidance system must have a special behavior and asymptotic stability or exponential stability of all states is not realistic. Thus, a new guidance law is developed based on the partial stability theorem in such a way that the behaviors of states in the closed-loop system are in conformity with a real guidance scenario that leads to collision. The performance of the proposed guidance law in terms of interception time and control effort is compared with the sliding mode guidance law by means of numerical simulations. PMID:21963401

An improved encoder alignment system is disclosed which provides an indication of the extent of misalignment and a measure of the rate at which the misalignment may be changing. The invention is adapted for use with a conventional encoder which provides a digital coarse word having at least significant bit and a digital fine word having a least significant bit and a most significant bit. The invention generates the exclusive or of the least significant bit of the coarse digital signal and the least significant bit of the fine digital signal to provide a first signal. The invention then generates the exclusive or of the first signal and the complement of the most significant bit of the fine digital signal to provide an output signal which represents the misalignment of the encoder.

Some 70 different molecular species have so far been detected variously in diffuse interstellar clouds, dense interstellar clouds, and circumstellar shells. Only simple (diatomic and triatomic) species exist in diffuse clouds because of the penetration of destructive UV radiations, whereas more complex (polyatomic) molecules survive in dense clouds as a result of the shielding against this UV radiation provided by dust grains. A current list of interstellar molecules is given together with a few other molecular species that have so far been detected only in circumstellar shells. Also listed are those interstellar species that contain rare isotopes of several elements. The gas phase ion chemistry is outlined via which the observed molecules are synthesized, and the process by which enrichment of the rare isotopes occurs in some interstellar molecules is described.

Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

Digital cameras would be colorblind if they did not have pixelated color filters integrated into their image sensors. Integration of conventional fixed filters, however, comes at the expense of an inability to modify the camera's spectral properties. Instead, we demonstrate a micropolarizer-based camera that can reconfigure its spectral response. Color is encoded into a linear polarization state by a chiral dispersive element and then read out in a single exposure. The polarization encoded color camera is capable of capturing three-color images at wavelengths spanning the visible to the near infrared. PMID:24690806

As early childhood teachers apply principles of guidance rather than punishment in their classrooms, they face the challenge of avoiding a slippage into traditional discipline practices and transcending the punitive aspects of discipline. Guidance is designed to teach children democratic life skills and therefore goes beyond discipline. Teachers…

Brain wiring is a highly intricate process in which trillions of neuronal connections are established. Its initial phase is particularly crucial in establishing the general framework of neuronal circuits. During this early step, differentiating neurons extend axons, which reach their target by navigating through a complex environment with extreme precision. Research in the past 20 years has unraveled a vast and complex array of chemotropic cues that guide the leading tip of axons, the growth cone, throughout its journey. Tight regulation of these cues, and of their receptors and signaling pathways, is necessary for the high degree of accuracy required during circuit formation. However, little is known about the nature of regulatory molecules or mechanisms fine-tuning axonal cue response. Here we review recent, and somewhat fragmented, research on the possibility that microRNAs (miRNAs) could be key fine-tuning regulatory molecules in axon guidance. miRNAs appear to shape long-range axon guidance, fasciculation and targeting. We also present several lines of evidence suggesting that miRNAs could have a compartmentalized and differential action at the cell soma, and within axons and growth cones. PMID:24672429

The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides this documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.

We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value. PMID:21296708

Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

Reviews the "Guidance Arrangements" consultation document issued with "Higher Still" (proposed new Scottish upper secondary curricula). Argues that the paper ignores the full implications for educational change in Higher Still and misses the opportunity for timely modernization of school guidance. Advocates a cross-curricular model of guidance…

The present invention relates to a program controlled apparatus for providing rapid calibration and update of sensor parameters in a push drill guidance apparatus which is remotely controllable from microprocessor circuitry. A special calibration program is set into nonvolatile memory for coaction with the control processor to compute sensor parameters for storage and recall during normal programmed guidance operation.

Secondary School Students face a lot of problems in their body as well as in mind due to puberty that tends to adolescence stage. Adolescence has peculiar characters of their own. They need proper Guidance and Counselling to tackle their own problems. Guidance is described as a counselling service to assist the individual in achieving self…

Ideas about discipline and guidance get extremely complex when they intersect with culture and oppression. Some groups of people who are targets of racism have to protect their children from the oppressive practices of racist individuals and institutions. Their methods of guidance and discipline may be different from those of groups for whom…

In 4 classroom experiments we investigated uses for technologies that automatically score student generated essays, concept diagrams, and drawings in inquiry curricula. We used the automatic scores to assign typical and research-based guidance and studied the impact of the guidance on student progress. Seven teachers and their 897 students…

This article was an introduction to a convention program presented at the Florida Personnel and Guidance Association Convention (Tampa, Nov., 1977) by Raymond Patouillet, shortly before his sudden death. It encapsulates his guidance philosophy, his understanding of the human condition, and his faith in the crucial role of the caring profession.…

A key part of a broad-based approach to career education in Australian schools is vocational/career guidance. Various vocational guidance programs have been developed for specific groups in Australian society, including work experience, caravans, and micrographics technology for the handicapped; pre-employment courses and a family education center…

Based on primary sources published in the Soviet Bloc, this article compares the stated goals of Marxist guidance with actual outcomes, and identifies the foundations of guidance in the Soviet Bloc in terms of Marxist philosophy and social doctrine. Current symptoms of ideological unrest in socialist society as exemplified by the suppressed reform…

Determining how axon guidance receptors transmit signals to allow precise pathfinding decisions is fundamental to our understanding of nervous system development and may suggest new strategies to promote axon regeneration after injury or disease. Signaling mechanisms that act downstream of four prominent families of axon guidance cues--netrins, semaphorins, ephrins, and slits--have been extensively studied in both invertebrate and vertebrate model systems. Although details of these signaling mechanisms are still fragmentary and there appears to be considerable diversity in how different guidance receptors regulate the motility of the axonal growth cone, a number of common themes have emerged. Here, we review recent insights into how specific receptors for each of these guidance cues engage downstream regulators of the growth cone cytoskeleton to control axon guidance. PMID:20452961

The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the "RH-TRU 72-B cask") and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a

The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to

The Autonomous Landing Guidance program is partly funded by the US Government under the Technology Reinvestment Project. The program consortium consists of avionics and other equipment vendors, airlines and the USAF. A Sextant Avionique HUD is used to present flight symbology in cursive form as well as millimeter wave radar imagery from Lear Astronics equipment and FLIR Systems dual-channel, forward-looking, infrared imagery. All sensor imagery is presented in raster form. A future aim is to fuse all imagery data into a single presentation. Sensor testing has been accomplished in a Cessna 402 operated by the Maryland Advanced Development Laboratory. Development testing is under way in a Northwest Airlines simulator equipped with HUD and image simulation. Testing is also being carried out using United Airlines Boeing 727 and USAF C-135C (Boeing 707) test aircraft. The paper addresses the technology utilized in sensory and display systems as well as modifications made to accommodate the elements in the aircraft. Additions to the system test aircraft include global positioning systems, inertial navigation systems and extensive data collection equipment. Operational philosophy and benefits for both civil and military users are apparent. Approach procedures have been developed allowing use of Category 1 ground installations in Category 3 conditions.

Future orbital observatories will require star trackers of extremely high precision. These sensors must maintain high pointing accuracy and pointing stability simultaneously with a low light level signal from a guide star. To establish the fine guidance sensing requirements and to evaluate candidate fine guidance sensing concepts, the Space Telescope Optical Telescope Assembly was used as the reference optical system. The requirements review was separated into three areas: Optical Telescope Assembly (OTA), Fine Guidance Sensing and astrometry. The results show that the detectors should be installed directly onto the focal surface presented by the optics. This would maximize throughput and minimize point stability error by not incoporating any additional optical elements.

Pathfinding by developing axons towards their proper targets is an essential step in establishing appropriate neuronal connections. Recent work involving cell culture assays and molecular biology strategies, including knockout animals, strongly indicates that a complex network of guidance signals regulates the formation of hippocampal connections during development. Outgrowing axons are routed towards the hippocampal formation by specific expression of long-range cues, which include secreted class 3 semaphorins, netrin 1 and Slit proteins. Local membrane- or substrate-anchored molecules, such as ligands of the ephrin A subclass, provide layer-specific positional information. Understanding the molecular mechanisms that underlie axonal guidance during hippocampal development might be of importance in making therapeutic use of sprouting fibers, which are produced following the loss of afferents in CNS lesion. PMID:11164941

The Text Encoding Initiative (TEI), an international collaboration aimed at producing a common encoding scheme for complex texts, examines the requirement for generality versus the requirement to handle specialized text types. Discusses how documents and users tax the limits of fixed schemes requiring flexible extensible encoding to support…

The purpose of this program guidance document is to provide technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the SARP and/or C of C shall govern. The C of C states: ''...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, ''Operating Procedures,'' of the application.'' It further states: ''...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, ''Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC approved, users need to be familiar with 10 CFR {section} 71.11, ''Deliberate Misconduct.'' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. This document details the instructions to be followed to operate, maintain, and test the RH-TRU 72-B packaging. This Program Guidance standardizes instructions for all users. Users shall follow these instructions. Following these instructions assures that operations are safe and meet the requirements of the SARP. This document is available on the Internet at: ttp://www.ws/library/t2omi/t2omi.htm. Users are responsible for ensuring they are using the current revision and change notices. Sites may prepare their own document using the word

A Martin-Marietta study comparing the application of laser, video, or RF sensors was conducted in 1982. The study concluded that video was the most attractive sensor (the video also could be used for operator monitoring). The Retro-Reflector field Tracker from the Solar Array Flight Experiment was chosen as a 'first generation' sensor and integrated with guidance algorithms for evaluation on the air-bearing vehicle. Results indicated that this sensor was not applicable for the noise environment posed by the multi-layer insulation used on most spacecraft. A 'second generation' sensor was developed to be used with a modified RMS target. This sensor utilized two sets of laser diodes to acquire three optically filtered targets. The targets were illuminated first with a 780 nanometer diode, followed by illumination with a 830 nm diode. The second digitized picture was subtracted from the first to get a low-noise image. The centroids of the retroreflectors were used then to uniquely derive target attitude and range. The sensor presently operates to 80 feet and within +/- 40 degrees in pitch and yaw. Sensor operability is a concern if the sun is within a +/- 40 degree cone angle to the target. The present sensor performance characteristics are less than 1 percent range error and less than 1 degree angle error. Future sensor development is anticipated to extend the operating range to 150 feet and reduce the cone angle of sensor inoperability to within +/- 10 degrees of direct sunlight. Performance improvements also are anticipated. TRW currently is developing a system that utilizes dual cameras with simultaneous diode illumination. Although further development is being pursued, the basic system has proven sound, and the sensor is essentially ready for application.

This guidance provides recommendations intended to assist in the development, evaluation and application of high quality environmental models that the Environmental Protection Agency uses to address environmental problems and to support regulatory activities. These guidelines wi...

Modular Reed-solomon encoder uses identical custom VLSI chips called "symbol slices." By cascading and properly interconnecting group of these chips, encoder is made for any desired error-correcting capability and interleaving level. VLSI encoder requires only one-tenth the number of chips required by conventional Reed-Solomon Circuit implemented with discrete IC's.

Optical encoders are commonly used in macroscopic machines to make precise measurements of distance and velocity by translating motion into a periodic signal. Here we show how Förster resonance energy transfer can be used to implement this technique at the single-molecule scale. We incorporate a series of acceptor dye molecules into self-assembling DNA, and the periodic signal resulting from unhindered motion of a donor-labeled molecular motor provides nanometer-scale resolution in milliseconds. PMID:20121107

We present a novel method, based on encoder mapping OCT imaging, for real-time guidance of core biopsy procedures. This method provides real-time feedback to the interventional radiologist, such that he/she can reorient the needle during the biopsy and sample the most representative area of the suspicious mass that is being investigated. This aspect is very important for tailoring therapy to the specific cancer based on biomarker analysis, which will become one of the next big advances in our search for the optimal cancer therapy. To enable individualized treatment, the genetic constitution and the DNA repair status in the affected areas is needed for each patient. Thus, representative sampling of the tumor is needed for analyzing various biomarkers, which are used as a tool to personalize cancer therapy. The encoder-based OCT enables samping of large size masses and provides full control on the imaging probe, which is passed through the bore of the biopsy guidance needle. The OCT image is built gradually, based on the feedback of an optical encoder which senses the incremental movement of the needle with a few microns resolution. Tissue mapping is independent of the needle speed, while it is advanced through the tissue. The OCT frame is analyzed in real-time and tissue cellularity is reported in a very simple manner (pie chart). Our preliminary study on a rabbit model of cancer has demonstrated the capability of this technology for accurately differentiating between viable cancer and heterogeneous or necrotic tissue.

This guide, for guidance personnel and teachers, is designed to provide ready access to current, practical programs, activities, and references for improving guidance programs. The resources are organized in four sections representing areas of basic concern for guidance personnel. Section 1 presents selected portions of guidance programs from…

Traces impetus for introduction of structured guidance into Scottish secondary schools. Identifies 1968 "Orange Paper" as first attempt to set out rationale for guidance. Describes how guidance is organized; outlines tasks of guidance teachers; and presents current developments, training requirements, and trends. (NEC)

Currently, in the field of guidance, relevant stakeholders including guidance practitioners, educators and policy makers, have identified progression for adults in education and employment as one of the key outcomes of educational guidance. Lifelong guidance is now inextricably linked with lifelong learning as a mechanism to enhance individual…

The various technologies presented herein relate to detecting nuclear material at a large stand-off distance. An imaging system is presented which can detect nuclear material by utilizing time encoded imaging relating to maximum and minimum radiation particle counts rates. The imaging system is integrated with a data acquisition system that can utilize variations in photon pulse shape to discriminate between neutron and gamma-ray interactions. Modulation in the detected neutron count rates as a function of the angular orientation of the detector due to attenuation of neighboring detectors is utilized to reconstruct the neutron source distribution over 360 degrees around the imaging system. Neutrons (e.g., fast neutrons) and/or gamma-rays are incident upon scintillation material in the imager, the photons generated by the scintillation material are converted to electrical energy from which the respective neutrons/gamma rays can be determined and, accordingly, a direction to, and the location of, a radiation source identified.

A device for position encoding of a rotating shaft in which a polygonal mirror having a number of facets is mounted to the shaft and a light beam is directed towards the facets is presented. The facets of the polygonal mirror reflect the light beam such that a light spot is created on a linear array detector. An analog-to-digital converter is connected to the linear array detector for reading the position of the spot on the linear array detector. A microprocessor with memory is connected to the analog-to-digital converter to hold and manipulate the data provided by the analog-to-digital converter on the position of the spot and to compute the position of the shaft based upon the data from the analog-to-digital converter.

A Linear Motion Encoding device for measuring the linear motion of a moving object is disclosed in which a light source is mounted on the moving object and a position sensitive detector such as an array photodetector is mounted on a nearby stationary object. The light source emits a light beam directed towards the array photodetector such that a light spot is created on the array. An analog-to-digital converter, connected to the array photodetector is used for reading the position of the spot on the array photodetector. A microprocessor and memory is connected to the analog-to-digital converter to hold and manipulate data provided by the analog-to-digital converter on the position of the spot and to compute the linear displacement of the moving object based upon the data from the analog-to-digital converter.

Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidancemolecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidancemolecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm. PMID:26625973

The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

The NASA Autonomous Guidance, Navigation and Control (GN&C) Bridging program is reviewed to demonstrate the program plan and GN&C systems for the Space Shuttle. The ascent CN&C system is described in terms of elements such as the general-purpose digital computers, sensors for the navigation subsystem, the guidance-system software, and the flight-control subsystem. Balloon-based and lidar wind soundings are used for operations assessment on the day of launch, and the guidance software is based on dedicated units for atmospheric powered flight, vacuum powered flight, and abort-specific situations. Optimization of the flight trajectories is discussed, and flight-control responses are illustrated for wavelengths of 500-6000 m. Alternate sensors are used for load relief, and adaptive GN&C systems based on alternate gain synthesis are used for systems failures.

The identification of bioactive compounds is a crucial step toward development of probes for chemical biology studies. Screening of DNA-encoded small molecule libraries (DELs) has emerged as a validated technology to interrogate vast chemical space. DELs consist of chimeric molecules composed of a low-molecular weight compound that is conjugated to a DNA identifier tag. They are screened as pooled libraries using selection to identify "hits." Screening of DELs has identified numerous bioactive compounds. Some of these molecules were instrumental in gaining a deeper understanding of biological systems. One of the main challenges in the field is the development of synthesis methodology for DELs. PMID:26820267

A flexible onboard encoder system was designed for the space shuttle. The following areas were covered: (1) implementation of the encoder design into hardware to demonstrate the various encoding algorithms/code formats, (2) modulation techniques in a single hardware package to maintain comparable reliability and link integrity of the existing link systems and to integrate the various techniques into a single design using current technology. The primary function of the command encoder is to accept input commands, generated either locally onboard the space shuttle or remotely from the ground, format and encode the commands in accordance with the payload input requirements and appropriately modulate a subcarrier for transmission by the baseband RF modulator. The following information was provided: command encoder system design, brassboard hardware design, test set hardware and system packaging, and software.

Title I of the Clean Air act Amendments of 1990 significantly changed requirements for regulatory agencies to prepare state implementation plans that demonstrate attainment of the ozone National Ambient Air Quality Standards. State agencies now are required to submit plans that show how they will meet the standards by their attainment date. EPA has published a series of guidance documents to assist states in preparing their plans. In addition, the agency is developing software to assist states in projecting emissions and tracking reductions. This article summarizes the guidance documents and software program.

The cerebellum receives its input from multiple precerebellar nuclei located in the brainstem, and sends processed information to other brain structures via the cerebellar deep neurons. Guidancemolecules that regulate the complex migrations of precerebellar neurons and the initial guidance of their leading processes have been identified. However, the molecules necessary for dorsal guidance of precerebellar axons to the developing cerebellum, or for guidance of decussating axons of the deep nuclei are not known. To determine whether Unc5c plays a role in the dorsal guidance of precerebellar and deep cerebellar axons, we studied axonal trajectories of these neurons in Unc5c-/- mice. Our results show that Unc5c is expressed broadly in the precerebellar and deep cerebellar neurons. Unc5c deletion disrupted long-range dorsal guidance of inferior olivary and pontine axons after crossing the midline. In addition, dorsal guidance of the axons from the medial deep cerebellar and external cuneate neurons was affected in Unc5c-/- mice, as were anterior migrations of pontine neurons. Coincident with the guidance defects of their axons, degeneration of neurons in external cuneate nucleus and subdivisions of inferior olivary nucleus was observed in Unc5c-/- mice. Lastly, transgenic expression of Unc5c in deep neurons and pontine neurons by the Atoh1 promoter rescued defects of the medial deep cerebellar and pontine axons observed in Unc5c-/- embryos, demonstrating that Unc5c acts cell autonomously in the guidance of these axons. Our results suggest that Unc5c plays a broad role in dorsal guidance of axons in the developing hindbrain. PMID:21307253

Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

Guidance-drama activity provides (a) crisp definitions of selected issues; (b) potent modeling from the characters in the play, the students actively engaged in the play, and the students involved in the discussions that follow the play; and (c) a technique for peer-led discussions on sensitive issues. This article gives precise definition to the…

A computerized information retrieval system has been designed to support the secondary school counseling effort. The system, entitled Total Guidance Information Support System (TGISS), runs on an IBM System/360 Model 65 facility and uses the IBM 2848 Display Control Unit. The software consists of an interactive communications program developed in…

Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

Fatigue cracking has been a principal cause of damage to North Sea structures and consequently considerable attention has been given to the development of guidance for the prediction of fatigue performance. The fatigue guidance of the Offshore Safety Division of the Health and Safety Executive (HSE) was recently revised and published, following a significant offshore industry review in the period 1987 to 1990, and is based on the results of a considerable amount of research and development work on the fatigue behavior of welded tubular and plated joints. As a result of this review, the revised fatigue guidance incorporates several new clauses and recommendations. The revised recommendations apply to joint classification, basic design S-N curves for welded joints and cast or forged steel components, the thickness effect, the effects of environment and the treatment of low and high stress ranges. Additionally, a new appendix on the derivation of stress concentration factors is included. The new clauses cover high strength steels, bolts and threaded connectors, moorings, repaired joints and the use of fracture mechanics analysis. This paper presents an overview of the revisions to the fatigue guidance, the associated background technical information and aspects of the fatigue behavior of offshore structures which are considered to require further investigation. 67 refs., 7 figs., 8 tabs.

Reviews the history and stages of development for career guidance in Singapore schools. Asserts that to meet the challenges of the new millennium, there is a need to train professional career counselors, develop indigenous resource materials, and promote a new concept of career development among students. (Contains 15 references.) (GCP)

Outlines the background, rationale, methodology, and outcomes of developing local lifelong guidance strategies in four geographic areas. Analyzes the main components of the strategies developed and addresses a number of issues relating to the process of strategy development. Explores implications for parallel work in other localities. (RJM)

This guidance presents a method and definitions for aggregating U.S. Department of Energy (DOE) waste into streams and treatability groups based on characteristic parameters that influence waste management technology needs. Adaptable to all DOE waste types (i.e., radioactive waste, hazardous waste, mixed waste, sanitary waste), the guidance establishes categories and definitions that reflect variations within the radiological, matrix (e.g., bulk physical/chemical form), and regulated contaminant characteristics of DOE waste. Beginning at the waste container level, the guidance presents a logical approach to implementing the characteristic parameter categories as part of the basis for defining waste streams and as the sole basis for assigning streams to treatability groups. Implementation of this guidance at each DOE site will facilitate the development of technically defined, site-specific waste stream data sets to support waste management planning and reporting activities. Consistent implementation at all of the sites will enable aggregation of the site-specific waste stream data sets into comparable national data sets to support these activities at a DOE complex-wide level.

In silent reading, short-memory tasks, such as semantic and syntactic processing, require a stage of phonetic encoding between visual representation and the actual extraction of meaning, and this encoding includes prosodic as well as segmental features. To test for this suprasegmental coding, an experiment was conducted in which subjects were…

This dissertation investigates advanced concepts in terminal missile guidance. The terminal phase of missile guidance usually lasts less than ten seconds and calls for very accurate maneuvering to ensure intercept. Technological advancements have produced increasingly sophisticated threats that greatly reduce the effectiveness of traditional approaches to missile guidance. Because of this, terminal missile guidance is, and will remain, an important and active area of research. The complexity of the problem and the desire for an optimal solution has resulted in researchers focusing on simplistic, usually linear, models. The fruit of these endeavors has resulted in some of the world's most advanced weapons systems. Even so, the resulting guidance schemes cannot possibly counter the evolving threats that will push the system outside the linear envelope for which they were designed. The research done in this dissertation greatly extends previous research in the area of optimal missile guidance. Herein it is shown that optimal missile guidance is fundamentally a pairing of an optimal guidance strategy and an optimal control strategy. The optimal guidance strategy is determined from a missile's information constraints, which are themselves largely determined from the missile's sensors. The optimal control strategy is determined by the missile's control constraints, and works to achieve a specified guidance strategy. This dichotomy of missile guidance is demonstrated by showing that missiles having different control constraints utilize the same guidance strategy so long as the information constraints are the same. This concept has hitherto been unrecognized because of the difficulty in developing an optimal control for the nonlinear set of equations that result from control constraints. Having overcome this difficulty by indirect means, evidence of the guidance strategy paradigm emerged. The guidance strategy paradigm is used to develop two advanced guidance laws. The new

We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones. PMID:25446944

The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals.

The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals. 32 figs.

Synthetic DNA has great propensity for efficiently and stably storing non-biological information. With DNA writing and reading technologies rapidly advancing, new applications for synthetic DNA are emerging in data storage and communication. Traditionally, DNA communication has focused on the encoding and transfer of complete sets of information. Here, we explore the use of DNA for the communication of short messages that are fragmented across multiple distinct DNA molecules. We identified three pivotal points in a communication-data encoding, data transfer & data extraction-and developed novel tools to enable communication via molecules of DNA. To address data encoding, we designed DNA-based individualized keyboards (iKeys) to convert plaintext into DNA, while reducing the occurrence of DNA homopolymers to improve synthesis and sequencing processes. To address data transfer, we implemented a secret-sharing system-Multiplexed Sequence Encoding (MuSE)-that conceals messages between multiple distinct DNA molecules, requiring a combination key to reveal messages. To address data extraction, we achieved the first instance of chromatogram patterning through multiplexed sequencing, thereby enabling a new method for data extraction. We envision these approaches will enable more widespread communication of information via DNA. PMID:27050646

Synthetic DNA has great propensity for efficiently and stably storing non-biological information. With DNA writing and reading technologies rapidly advancing, new applications for synthetic DNA are emerging in data storage and communication. Traditionally, DNA communication has focused on the encoding and transfer of complete sets of information. Here, we explore the use of DNA for the communication of short messages that are fragmented across multiple distinct DNA molecules. We identified three pivotal points in a communication—data encoding, data transfer & data extraction—and developed novel tools to enable communication via molecules of DNA. To address data encoding, we designed DNA-based individualized keyboards (iKeys) to convert plaintext into DNA, while reducing the occurrence of DNA homopolymers to improve synthesis and sequencing processes. To address data transfer, we implemented a secret-sharing system—Multiplexed Sequence Encoding (MuSE)—that conceals messages between multiple distinct DNA molecules, requiring a combination key to reveal messages. To address data extraction, we achieved the first instance of chromatogram patterning through multiplexed sequencing, thereby enabling a new method for data extraction. We envision these approaches will enable more widespread communication of information via DNA. PMID:27050646

Describes the role of The National Society of Professional Engineers (NSPE) in providing guidance activities for students. Discusses structional organization, goals, and guidance activities for engineering and technical and professional societies. (MA)

Illustrates the content, process, and group dynamics of Activity Group Guidance. Describes and evaluates a comprehensive Activity Group Guidance program. Gives specific suggestions to counselors who wish to start Activity Groups. (Author)

Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)--fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media. PMID:12618846

In Europe there is no common quality assurance framework for the delivery of guidance in higher education. Using a case study approach in four university career guidance services in England, France and Spain, this article aims to study how quality is implemented in university career guidance services in terms of strategy, standards and models,…

This handbook describes a series of procedures for establishing school guidance and counseling programs in Idaho based on the Missouri Comprehensive Guidance Program model developed by Dr. Norman Gysbers. It begins with a conceptual framework and moves through the development, evaluation, and refinement steps of setting guidance programs in Idaho…

This report reviews and analyzes the development and status of computer-assisted-guidance (CAG) systems. In terms of eight major topics which are introduced in a discussion of guidance and the computer, the report discusses the capabilities of computers in reference to other resources for guidance and describes and differentiates various CAG…

A laboratory and field test program was conducted to quantify the optical navigation parameters of the Mariner vidicons. A scene simulator and a camera were designed and built for vidicon tests under a wide variety of conditions. Laboratory tests characterized error sources important to the optical navigation process and field tests verified star sensitivity and characterized comet optical guidance parameters. The equipment, tests and data reduction techniques used are described. Key test results are listed. A substantial increase in the understanding of the use of selenium vidicons as detectors for spacecraft optical guidance was achieved, indicating a reduction in residual offset errors by a factor of two to four to the single pixel level.

The precision of axonal pathfinding and the accurate formation of functional neural circuitry are crucial for an organism during development as well as during adult central and peripheral nerve regeneration. While chemical cues are believed to be primarily responsible for axonal pathfinding, we hypothesize that forces due to localized fluid flow may directly affect neuronal guidance during early organ development. Here, we report direct evidence of fluid flow influencing axonal migration, producing turning angles of up to 90°. Microfluidic flow simulations indicate that an axon may experience significant bending force due to cross-flow, which may contribute to the observed axonal turning. This method of flow-based guidance was successfully used to fasciculate one advancing axon onto another, showcasing the potential of this technique to be used for the formation of in vitro neuronal circuits.

Teleautonomous guidance (TG), a technique for the remote guidance of fast mobile robots, has been developed and implemented. With TG, the mobile robot follows the general direction prescribed by an operator. However, if the robot encounters an obstacle, it autonomously avoids collision with that obstacle while trying to match the prescribed direction as closely as possible. This type of shared control is completely transparent and transfers control between teleoperation and autonomous obstacle avoidance gradually. TG allows the operator to steer vehicles and robots at high speeds and in cluttered environments, even without visual contact. TG is based on the virtual force field (VFF) method, which was developed earlier for autonomous obstacle avoidance. The VFF method is especially suited to the accommodation of inaccurate sensor data (such as that produced by ultrasonic sensors) and sensor fusion, and allows the mobile robot to travel quickly without stopping for obstacles.

Growth cones are able to navigate over long distances to find their appropriate target by following guidance cues that are often presented to them in the form of an extracellular gradient. These external cues are converted into gradients of specific signaling molecules inside growth cones, while at the same time these internal signals are amplified. The amplified instruction is then used to generate asymmetric changes in the growth cone turning machinery so that one side of the growth cone migrates at a rate faster than the other side, and thus the growth cone turns toward or away from the external cue. This review examines how signal specification and amplification can be achieved inside the growth cone by multiple second messenger signaling pathways activated downstream of guidance cues. These include the calcium ion, cyclic nucleotide, and phosphatidylinositol signaling pathways. PMID:24285606

Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (∼10–20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. PMID:20055680

Central to `multimedia' image processing is the desire to encode computer graphics data into a standard television signal, complete with line, field, and color subcarrier synchronizing information. The numerous incompatibilities between television and computer display standards render this operation far less trivial than it sounds to anyone who hasn't worked with both types of signals. To simplify the task of encoding computer graphics signals into standard NTSC (North America and Japan) or PAL (most of Europe) television format for display, broadcast, or recording, TRW LSI Products Inc. has introduced the two newest members of it multimedia integrated circuit family, the TMC22090 and TMC22190 digital video encoders.

The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 12.5 km of the pre-designated parachute deploy coordinates. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and entry delivery errors are presented.

The development of a multicellular organism involves time-dependent changes in molecular and cellular states; therefore 'time' is an indispensable mathematical parameter of ontogenesis. Regardless of their inextricable relationship, there is a limited number of events for which the output of developmental phenomena primarily uses temporal cues that are generated through multilevel interactions between molecules, cells, and tissues. In this review, we focus on neural stem cells, which serve as a faithful decoder of temporal cues to transmit biological information and generate specific output in the developing nervous system. We further explore the identity of the temporal information that is encoded in neural development, and how this information is decoded into various cellular fate decisions. PMID:26748623

Reduced short-term memory (STM) capacity has been reported for sign as compared to speech when items have to be recalled in a specific order. This difference has been attributed to a more precise and efficient serial position encoding in verbal STM (used for speech) than visuo-spatial STM (used for sign). We tested in the present investigation whether the reduced STM capacity with signs stems from a lack of positional encoding available in verbal STM. Error analyses reported in prior studies have revealed that positions are defined in verbal STM by distance from both the start and the end of the sequence (both-edges positional encoding scheme). Our analyses of the errors made by deaf participants with finger-spelled letters revealed that the both-edges positional encoding scheme underlies the STM representation of signs. These results indicate that the cause of the STM disadvantage is not the type of positional encoding but rather the difficulties in binding an item in visuo-spatial STM to its specific position in the sequence. Both-edges positional encoding scheme could be specific of sign, since it has not been found in visuo-spatial STM tasks conducted with hearing participants. PMID:27244095

The core electron problem of atoms in chemical graph studies has always been considered as a minor problem. Usually, chemical graphs had to encode just a small set of second row atoms, i.e., C, N, O, and F, thus, graph and, in some cases, pseudograph concepts were enough to "graph" encode the molecules at hand. Molecular connectivity theory, together with its side-branch the electrotopological state, introduced two "ad hoc" algorithms for the core electrons of higher-row atoms based, mainly, on quantum concepts alike. Recently, complete graphs, and, especially, odd complete graphs have been introduced to encode the core electrons of higher-row atoms. By the aid of these types of graphs a double-valued algorithm has been proposed for the valence delta, deltav, of any type of atoms of the periodic table with a principal quantum number n > or =2. The new algorithm is centered on an invariant suggested by the hand-shaking theorem, and the values it gives rise to parallel in some way the values derived by the aid of the two old "quantum" algorithms. A thorough comparative analysis of the newly proposed algorithms has been undertaken for atoms of the group 1A-7A of the periodic table. This comparative study includes the electronegativity, the size of the atoms, the first ionization energy, and the electron affinity. The given algorithm has also been tested with sequential complete graphs, while the even complete graphs give rise to conceptual difficulties. QSAR/QSPR studies do not show a clear-cut preference for any of the two values the algorithm gives rise to, even if recent results seem to prefer one of the two values. PMID:14741009

Olfaction begins with the transduction of the information carried by odorants into electrical signals in olfactory receptor cells (ORCs). The binding of odor molecules to specific receptor proteins on the ciliary surface of ORCs induces the receptor potentials. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na+ currents and T-type Ca2+ currents in the somatic membrane. Isolated ORCs, which have lost their cilia during the dissociation procedure, are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:12871762

Cell migration and guidance are complex processes required for morphogenesis, the formation of tumor metastases, and the progression of human cancer. During migration, guidancemolecules induce cell directionality and movement through complex intracellular mechanisms. Expression of these molecules has to be tightly regulated and their signals properly interpreted by the receiving cells so as to ensure correct navigation. This molecular control is fundamental for both normal morphogenesis and human disease. The Hedgehog (Hh) signaling pathway is evolutionarily conserved and known to be crucial for normal cellular growth and differentiation throughout the animal kingdom. The relevance of Hh signaling for human disease is emphasized by its activation in many cancers. Here, I review the current knowledge regarding the involvement of the Hh pathway in cell migration and guidance during Drosophila development and discuss its implications for human cancer origin and progression. PMID:26445062

Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include an amino acid sequence, and variants and fragments thereof, for an antipathogenic polypeptide that was isolated from a fungal fermentation broth. Nucleic acid molecules that encode the antipathogenic polypeptides of the invention, and antipathogenic domains thereof, are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention are also disclosed.

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans. PMID:11257122

This report summarizes the work done at Lawrence Livermore National Laboratory for the Oligonucleotide and Long Polymeric DNA Encoding project, part of the Microelectronic Bioprocesses Program at DARPA. The goal of the project was to develop a process by which long (circa 10,000 base-pair) synthetic DNA molecules could be synthesized in a timely and economic manner. During construction of the long molecule, errors in DNA sequence occur during hybridization and/or the subsequent enzymatic process. The work done on this project has resulted in a novel synthesis scheme that we call the parallel pyramid synthesis protocol, the development of a suit of computational tools to minimize and quantify errors in the synthesized DNA sequence, and experimental proof of this technique. The modeling consists of three interrelated modules: the bioinformatics code which determines the specifics of parallel pyramid synthesis for a given chain of long DNA, the thermodynamics code which tracks the products of DNA hybridization and polymerase extension during the later steps in the process, and the kinetics model which examines the temporal and spatial processes during one thermocycle. Most importantly, we conducted the first successful syntheses of a gene using small starting oligomers (tetramers). The synthesized sequence, 813 base pairs long, contained a 725 base pair gene, modified green fluorescent protein (mGFP), which has been shown to be a functional gene by cloning into cells and observing its green fluorescent product.

Visual search for targets among distractors is more efficient if attention can be guided to targets by attributes like color. In real-world search, we guide attention using information about surfaces. (e.g., paintings are on walls). We compare “classic” color guidance to surface guidance in “scenes” of cubes. When a target can lie on one of many surfaces, color guidance is effective but surface guidance is not (Exp. 1-3). Surface guidance works when cued surfaces are coplanar (Exp. 4) or few in number (Exp. 5). We speculate that surface guidance is slow and limited to very few surfaces at one time. PMID:19236891

This report describes a requirements specification written in the RSML-e language for the mode logic of a Flight Guidance System of a typical regional jet aircraft. This model was created as one of the first steps in a five-year project sponsored by the NASA Langley Research Center, Rockwell Collins Inc., and the Critical Systems Research Group of the University of Minnesota to develop new methods and tools to improve the safety of avionics designs. This model will be used to demonstrate the application of a variety of methods and techniques, including safety analysis of system and subsystem requirements, verification of key properties using theorem provers and model checkers, identification of potential sources mode confusion in system designs, partitioning of applications based on the criticality of system hazards, and autogeneration of avionics quality code. While this model is representative of the mode logic of a typical regional jet aircraft, it does not describe an actual or planned product. Several aspects of a full Flight Guidance System, such as recovery from failed sensors, have been omitted, and no claims are made regarding the accuracy or completeness of this specification.

Presented in this report are the recommendations of two expert groups, the Technical Guidance/Competence Working Group of the US Agency for International Development's Maximizing Access and Quality Initiative and the World Health Organization's Family Planning and Population Unit, regarding currently available family planning methods. The former group addressed key biomedical questions and formulated recommendations about 11 groups of family planning methods: combined oral contraceptives, progestin-only pills during breast feeding, progestin-only injectables, combined injectable contraceptives, Norplant implants, copper-bearing IUDs, tubal occlusion, vasectomy, lactational amenorrhea method, natural family planning, and barrier methods. A table presents the relative importance, by method, of procedures such as pelvic exam, blood pressure reading, breast exam, and screening for sexually transmitted diseases and cervical cancer. The medical eligibility recommendations for each method are also presented in tabular form, with four categories for temporary methods: 1) no restrictions on use, 2) advantages generally outweigh theoretical or proven risks, 3) theoretical or proven risks usually outweigh the advantages, and 4) unacceptable health risks. Included among the 41 conditions for which eligibility criteria are specified are age, smoking, thromboembolic disorder, headaches, irregular vaginal bleeding, family history of breast cancer, obesity, drug interactions, parity, breast feeding, postpartum, and postabortion. The new guidance presented in this report enables providers to give family planning clients expanded contraceptive choices while ensuring method safety and effectiveness. PMID:9342775

The aerocapture is a promising technique for the future human interplanetary missions. The Mars Sample Return was initially based on an insertion by aerocapture. A CNES orbiter Mars Premier was developed to demonstrate this concept. Mainly due to budget constraints, the aerocapture was cancelled for the French orbiter. A lot of studies were achieved during the three last years to develop and test different guidance algorithms (APC, EC, TPC, NPC). This work was shared between CNES and NASA, with a fruitful joint working group. To finish this study an evaluation campaign has been performed to test the different algorithms. The objective was to assess the robustness, accuracy, capability to limit the load, and the complexity of each algorithm. A simulation campaign has been specified and performed by CNES, with a similar activity on the NASA side to confirm the CNES results. This evaluation has demonstrated that the numerical guidance principal is not competitive compared to the analytical concepts. All the other algorithms are well adapted to guaranty the success of the aerocapture. The TPC appears to be the more robust, the APC the more accurate, and the EC appears to be a good compromise.

Recent progress in the development of a gravity-sensor-based instrument for determining the elevation angle of DSN antennas is described. The benefits of such a system include the capability to locate the Gravity Referenced Elevation Encoder (GREE) directly on the primary reflector (thus bypassing structural flexure and deformation error sources), anticipated lower maintenance costs compared to the present gimbal encoders, direct replaceability, or supplementation of the present gimbal encoders and the utilization of off-the-shelf components to construct the GREE. This article includes a description of the nominal GREE design. Test results on a laboratory breadboard model are given. Rigid-body dynamics of the GREE are derived and the simulated performance in response to measured antenna vibrations is given.

Recent progress in the development of a gravity-sensor-based instrument for determining the elevation angle of DSN antennas is described. The benefits of such a system include the capability to locate the Gravity Referenced Elevation Encoder (GREE) directly on the primary reflector (thus bypassing structural flexure and deformation error sources), anticipated lower maintenance costs compared to the present gimbal encoders, direct replaceability, or supplementation of the present gimbal encoders and the utilization of off-the-shelf components to construct the GREE. This article includes a description of the nominal GREE design. Test results on a laboratory breadboard model are given. Rigid-body dynamics of the GREE are derived and the simulated performance in response to measured antenna vibrations is given.

More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli. PMID:27336733

More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli. PMID:27336733

The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

A novel guidance algorithm for launch vehicle ascent to the desired mission orbit is proposed. The algorithm uses total specific energy and orbital angular momentum as new state vector parameters. These parameters are ideally suited for the ascent guidance task, since the guidance algorithm steers the launch vehicle along a pre-flight optimal trajectory in energy angular momentum space. The guidance algorithm targets apogee, perigee, inclination and right ascension of ascending node. Computational complexities are avoided by eliminating time in the guidance computation and replacing it with angular momentum magnitude. As a result, vehicle acceleration, mass, thrust, length of motor burns, and staging times are also eliminated from the pitch plane guidance calculations. The algorithm does not involve launch vehicle or target state propagation, which results in minimal computational effort. Proof of concept of the new algorithm is presented using several numerical examples that illustrate performance results.

The present doctoral thesis analyses the potential of technological advances in electronics, telematics and communications for their application in agriculture. Research has been carried out and some prototypes have been developed in four stages: In a first phase, it has been carried out the analysis and development of guidance assistance devices. It has been carried out the development of a microcontroller based device which has been patented by the author of this thesis and later, has been developed and commercialized by the company GMV Sistemas. In a second phase, it has been developed a module of distance guidance which allows the remote driving of an agricultural tractor. There have been made the mechanical modifications in a tractor and the necessary hardware has been installed in order to allow the remote control of the tractor steering. The laptop receives the guidance instructions by means of wireless communication from the computer installed in the base. In a third phase, there have been developed two autonomous guidance systems, one by means of GPS and the other by means of Computer Vision, using as base the platform developed in the previous phase. It is incorporated a module of path generation from the plot outline. With this trajectory, the tractor is able to do most of the farming work in a plot without the participation of the driver. The last phase has been developed at the same time than the previous ones and it is located in Precision Agriculture. In this phase it has been carried out the performance of a centrifugal spreader of fertilizer and it has been developed an application for the generation in a precise way of fertilizer maps. The carried out studies have produced real developments implanted on the machinery of the author's farm. The development of the work has been carried out on a software platform with modules which are intercommunicated between them, because a large part of the developed applications have a common base of work. This

Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit, in which the time delay inherent with communication will make remote guidance impractical.

During development, neurons are guided to their targets by short- and long-range attractive and repulsive cues. MICAL, a large multidomain protein, is required for the combined action of semaphorins and plexins in axon guidance. Here, we present the structure of the N-terminal region of MICAL (MICAL{sub fd}) determined by x-ray diffraction to 2.0 Angstrom resolution. The structure shows that MICAL{sub fd} is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICALfd is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H{sub 2}O{sub 2} (Km, NAPDH = 222 {micro}M; k{sub cat} = 77 sec{sup -1}), a molecule with known signaling properties. We propose that the H{sub 2}O{sub 2} produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.

During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling. Here, we show that UNC-40, SAX-3 and the SYD-1 RhoGAP-like protein function interdependently to regulate the MIG-2 (Rac) GTPase in the HSN axon of C. elegans. We find that SYD-1 mediates an UNC-6 (netrin) independent UNC-40 activity to promote ventral axon guidance. Genetic analysis suggests that SYD-1 function in axon guidance requires both UNC-40 and SAX-3 activity. Moreover, the cytoplasmic domains of UNC-40 and SAX-3 bind to SYD-1 and SYD-1 binds to and negatively regulates the MIG-2 (Rac) GTPase. We also find that the function of SYD-1 in axon guidance is mediated by its phylogenetically conserved C isoform, indicating that the role of SYD-1 in guidance is distinct from its previously described roles in synaptogenesis and axonal specification. Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals. PMID:25876065

This study explores how infants encode an object's spatial extent. We habituated 6.5-month-old infants to a dowel inside a container and then tested whether they dishabituate to a change in absolute size when the relation between dowel and container is held constant (by altering the size of both container and dowel) and when the relation changes…

Circuits that include compensation circuitry time a capacitance relative to a reference voltage so that a digital presentation occurs that is representative of the positional condition of the mechanical shaft being monitored. This circuitry may be employed in multiples to furnish binary encoding of a number of rotating devices simultaneously.

The demand for extensive reusability of large language text collections for natural languages processing research requires development of standardized encoding formats. Such formats must be capable of representing different kinds of information across the spectrum of text types and languages, capable of representing different levels of…

Anecdotally, surgeons sometimes observe large errors when using image guidance in endonasal surgery. We hypothesize that one contributing factor is the possibility that operating room personnel might accidentally bump the optically tracked rigid body attached to the patient after registration has been performed. In this paper we explore the registration error at the skull base that can be induced by simulated bumping of the rigid body, and find that large errors can occur when simulated bumps are applied to the rigid body. To address this, we propose a new fixation method for the rigid body based on granular jamming (i.e. using particles like ground coffee). Our results show that our granular jamming fixation prototype reduces registration error by 28%-68% (depending on bump direction) in comparison to a standard Brainlab reference headband.

The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides the documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

The longwall guidance and control (G&C) system was evaluated to determine which systems and subsystems lent themselves to automatic control in the mining of coal. The upper coal/shale interface was identified as the reference for a vertical G&C system, with two sensors (the natural backgound and the sensitized pick) being used to locate and track this boundary. In order to insure a relatively smooth recession surface (roof and floor of the excavated seam), a last and present cut measuring instrument (acoustic sensor) was used. Potentiometers were used to measure elevations of the shearer arms. The intergration of these components comprised the vertical control system (pitch control). Yaw and roll control were incorporated into a face alignment system which was designed to keep the coal face normal to its external boundaries. Numerous tests, in the laboratory and in the field, have confirmed the feasibility of automatic horizon control, as well as determining the face alignment.

The Orion vehicle is being designed to provide nominal crew transport to the lunar transportation stack in low Earth orbit, crew abort prior during transit to the moon, and crew return to Earth once lunar orbit is achieved. Design of guidance and navigation algorithms to perform maneuvers in support of these functions is dependent on the support provided by navigation infrastructure, the performance of the onboard GN&C system, and the choice of trajectory maneuver methodology for outbound and return mission phases. This paper documents the preliminary integrated analyses performed by members of the Orion Orbit GN&C System team investigating the navigation update accuracy of a modern equivalent to the Apollo era ground tracking network and the expected onboard dispersion and navigation errors during a lunar mission using a linear covariance error analysis technique.

The Rendezvous and Proximity Operations Program (RPOP) is real-time guidance, navigation, and control (GN&C) domain piloting-aid software that provides 3D Orbiter graphics and runs on the Space Shuttle's Criticality-3 Payload and General Support Computer (PGSC) in the crew cockpit. This software provides the crew with Situational Awareness during the rendezvous and proximity operations phases of flight. RPOP can be configured from flight to flight, accounting for mission-specific flight scenarios and target vehicles, via initialization load (I-load) data files. The software provides real-time, automated, closed-loop guidance recommendations and the capability to integrate the crew s manual backup techniques. The software can bring all relative navigation sensor data, including the Orbiter's GPC (general purpose computer) data, into one central application to provide comprehensive situational awareness of the rendezvous and proximity operations trajectory. RPOP also can separately maintain trajectory estimates (past, current, and predicted) based on certain data types and co-plot them, in order to show how the various navigation solutions compare. RPOP s best estimate of the relative trajectory is determined by a relative Kalman filter processing data provided by the sensor suite s most accurate sensor, the trajectory control sensor (TCS). Integrated with the Kalman filter is an algorithm that identifies the reflector that the TCS is tracking. Because RPOP runs on PC laptop computers, the development and certification lifecycles are more agile, flexible, and cheaper than those that govern the Orbiter FSW (flight software) that runs in the GPC. New releases of RPOP can be turned around on a 3- to 6-month template, from new Change Request (CR) to certification, depending on the complexity of the changes.

EPA headquarters and a national site assessment workgroup produced this guidance for Regional, State, and contractor staff who manage or perform preliminary assessments (PAs). EPA has focused this guidance on the types of sites and site conditions most commonly encountered. The PA approach described in this guidance is generally applicable to a wide variety of sites. However, because of the variability among sites, the amount of information available, and the level of investigative effort required, it is not possible to provide guidance that is equally applicable to all sites. PA investigators should recognize this and be aware that variation from this guidance may be necessary for some sites, particularly for PAs performed at Federal facilities, PAs conducted under EPA`s Environmental Priorities Initiative (EPI), and PAs at sites that have previously been extensively investigated by EPA or others. The purpose of this guidance is to provide instructions for conducting a PA and reporting results. This guidance discusses the information required to evaluate a site and how to obtain it, how to score a site, and reporting requirements. This document also provides guidelines and instruction on PA evaluation, scoring, and the use of standard PA scoresheets. The overall goal of this guidance is to assist PA investigators in conducting high-quality assessments that result in correct site screening or further action recommendations on a nationally consistent basis.

This article summarizes the work of a diverse group of researchers and practitioners from 5 continents on "Vocational Guidance Requests Within the International Scene" presented in the discussion group at a symposium of the International Association for Educational and Vocational Guidance, the Society for Vocational Psychology, and the National…

In mammals, sperm guidance in the oviduct appears essential for successful sperm arrival at the oocyte. Hitherto, three different potential sperm guidance mechanisms have been recognized: thermotaxis, rheotaxis, and chemotaxis, each of them using specific stimuli – a temperature gradient, fluid flow, and a chemoattractant gradient, respectively. Here, we review sperm behavioral in these mechanisms and indicate commonalities and differences between them. PMID:25999361

A brief study conducted for the Further Education Unit, Great Britain, defined the competencies associated with educational guidance for adults. The objective was to develop a qualification for educational guidance workers with adults. The project provided an example of applying a competence model to a "higher level" interpersonal field of work.…

Recent Further Education Unit (FEU) research has provided clear evidence of technical college students' needs for career and educational guidance throughout their program of study. Inhouse technical college guidance services to individuals and institutions offer a number of benefits to both students receiving the services and the institutions…

The purpose of this exploratory-descriptive study was to examine how guidance counsellors in the province of Newfoundland and Labrador would handle a specific verbal-relational bullying incident. Also of interest was guidance counsellor involvement and training in bullying programmes and Positive Behaviour Supports. Data for this study was…

Three practical ideas that can be implemented in elementary schools are given: (1) a guidance committee (composed of representatives from each grade level and an administrator) to facilitate involvement in the school guidance program; (2) field trips to introduce students to the world of work and to establish motivations for learning subject…

Social benefits can be thought of as aggregates of individual benefits, though with possible "snowball" effects. Potential social benefits of career guidance fall into the following two main categories: reducing social exclusion and enhancing social development. Guidance is a way of making the structure of society work, by linking individual needs…

Deregulation of the LEA Careers Service followed by the establishment of the National Assembly for Wales in 1999 led, through consultation, to the establishment of a bi-lingual all-age career guidance service under the banner of Careers Wales. The article traces the history of career guidance in Wales from 1974, showing how it has taken a very…

Career guidance may have the potential to promote public health by contributing positively to both the prevention of mental health conditions and to population level well-being. The policy implications of this possibility have received little attention. Career guidance agencies are well placed to reach key target groups. Producing persuasive…

This book provides educators, counselors, policy makers, and community members with information about the state of the art of federal and state policy in guidance and counseling. The two chapters in part 1, Overview, are: "Foundations for Policy in Guidance and Counseling: An Introduction", by Edwin L. Herr and Nancy M. Pinson; and "A Counselor…

The authors identify and discuss the main themes from the discourse on the internationalization of educational and vocational guidance at the 2004 "Symposium on International Perspectives on Career Development," co sponsored by the International Association for Educational and Vocational Guidance and the National Career Development Association.…

The purposes of this article are twofold. First, it considers the policy links between guidance and lifelong learning, highlighting in particular the implications of findings from a recent study by the Organisation for Economic Co-operation and Development (OECD). Secondly, it critically compares two approaches to workplace guidance about…

Several recently developed measurement instruments, the General Aptitude Test Battery (GATB), the Comparative Guidance and Placement Program (CGP), the Kuder Occupational Interest Survey (DD), the Ohio Vocational Interest Survey (OVIS), and the Gordon Occupational Check List, are considered in connection with guidance testing for occupational…

The purpose of this column is to discuss, describe and disseminate information regarding career guidance principles and practices in the elementary schools. Specifically the activities of the Developmental Career Guidance Projects in inner city Detroit are described. The activities emphasize action involvement of children while didactic learning…

In October, 1967, 100 invited participants representing all aspects of guidance, education, school administration, counselor education, psychology, and interested government agencies in Pennsylvania met for three days to listen, think, discuss, and hopefully develop some recommendations for those who want a better program of elementary guidance.…

North Carolina State Dept. of Public Instruction, Raleigh. Occupational Research Unit.

The project had three goals: to increase the supply of elementary counselors in North Carolina, to provide guidance services to seventeen elementary schools in a satisfactory manner so the program would be adopted after expiration of the project, and to provide systematic guidance services for children in grades one through six. Four full time…

This document provides the guidance necessary to transmit to DOE`s Office of Scientific and Technical Information (OSTI) an encoded bibliographic record that conforms to International Standard ISO 8879, Information Processing -- Text and office systems -- Standard Generalized Markup Language (SGML). Included in this document are element and attribute tag definitions, sample bibliographic records, the bibliographic document type definition, and instructions on how to transmit a bibliographic record electronically to OSTI.

Onboard optical approach guidance measurements for spin-stabilized Pioneer-type spacecraft are discussed. Approach guidance measurement accuracy requirements are outlined. The application concept and operation principle of the V-slit star tracker are discussed within the context of approach guidance measurements and measurables. It is shown that the accuracy of onboard optical approach guidance measurements is inherently coupled to the stability characteristics of the spacecraft spin axis. Geometrical and physical measurement parameters are presented for Pioneer entry probe missions to Uranus via Jupiter or Saturn flyby. The impact of these parameters on both sensor instrumentation and measurement system design is discussed. The need for sensing extended objects is shown. The feasibility of implementing an onboard approach guidance measurement system for Pioneer-type spacecraft is indicated. Two Pioneer 10 onboard measurement experiments performed in May-June 1974 are described.

The specifications for proposed space transportation systems are placing more emphasis on developing reusable avionics subsystems which have the capability to respond to vehicle evolution and diverse missions while at the same time reducing the cost of ground support for mission planning, contingency response and verification and validation. An innovative approach to meeting these goals is to specify the guidance problem as a multi-point boundary value problen and solve that problem using modern control theory and nonlinear constrained optimization techniques. This approach has been implemented as Gamma Guidance (Hardtla, 1978) and has been successfully flown in the Inertial Upper Stage. The adaptive guidance algorithm described in this paper is a generalized formulation of Gamma Guidance. The basic equations are presented and then applied to four diverse aerospace vehicles to demonstrate the feasibility of using a reusable, explicit, adaptive guidance algorithm for diverse applications and vehicles.

The X-33 Advanced Technology Demonstrator is a half-scale prototype developed to test the key technologies needed for a full-scale single-stage reusable launch vehicle (RLV). The X-33 is a suborbital vehicle that will be launched vertically, and land horizontally. The goals of this research were to develop an alternate entry guidance scheme for the X-33 in parallel to the actual X-33 entry guidance algorithms, provide comparative and complementary study, and identify potential new ways to improve entry guidance performance. Toward these goals, the nominal entry trajectory is defined by a piecewise linear drag-acceleration-versus-energy profile, which is in turn obtained by the solution of a semi-analytical parameter optimization problem. The closed-loop guidance is accomplished by tracking the nominal drag profile with primarily bank-angle modulation on-board. The bank-angle is commanded by a single full-envelope nonlinear trajectory control law. Near the end of the entry flight, the guidance logic is switched to heading control in order to meet strict conditions at the terminal area energy management interface. Two methods, one on ground-track control and the other on heading control, were proposed and examined for this phase of entry guidance where lateral control is emphasized. Trajectory dispersion studies were performed to evaluate the effectiveness of the entry guidance algorithms against a number of uncertainties including those in propulsion system, atmospheric properties, winds, aerodynamics, and propellant loading. Finally, a new trajectory-regulation method is introduced at the end as a promising precision entry guidance method. The guidance principle is very different and preliminary application in X-33 entry guidance simulation showed high precision that is difficult to achieve by existing methods.

We have developed an extremely small integrated microencoder whose sides are less than 1 mm long. It is 1/100 the size of conventional encoders. This microencoder consists of a laser diode, monolithic photodiodes, and fluorinated polyimide waveguides with total internal reflection mirrors. The instrument can measure the relative displacement between a grating scale and the encoder with a resolution of the order of 0.01 microm; it can also determine the direction in which the scale is moving. By using the two beams that were emitted from the two etched mirrors of the laser diode, by monolithic integration of the waveguide and photodiodes, and by fabrication of a step at the edge of the waveguide, we were able to eliminate conventional bulky optical components such as the beam splitter, the quarter-wavelength plate, bulky mirrors, and bulky photodetectors. PMID:18324228

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE. PMID:26605881

Space shuttle guidance, navigation, and control design equations are presented. The space-shuttle mission includes three relatively distinct guidance phases which are discussed; atmospheric boost, which is characterized by an adaptive guidance law; extra-atmospheric activities; and re-entry activities, where aerodynamic surfaces are the principal effectors. Guidance tasks include pre-maneuver targeting and powered flight guidance, where powered flight is defined to include the application of aerodynamic forces as well as thruster forces. A flow chart which follows guidance activities throughout the mission from the pre-launch phase through touchdown is presented. The main guidance programs and subroutines used in each phase of a typical rendezvous mission are listed. Detailed software requirements are also presented.

Nonconjugative plasmids encoding sulfanilamide (Sa) resistance were demonstrated at a high frequency in Shigella and Escherichia coli strains resistant to sulfanilamide. These Sa plasmids were all compatible with the standard plasmids used in compatibility testing. The sizes of seven Sa plasmids were measured by electron microscopy and ranged from 1.79 to 2.08 μm, corresponding to 3.5 to 3.9 megadaltons. Images PMID:334067

The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements-including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication-in the model organisms Drosophila melanogaster and Caenorhabditis elegans. During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems. PMID:26133010

Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

This paper assesses a preliminary guidance and targeting strategy for accomplishing Skip-Entry (SE) flight during a lunar return-capsule entry flight. One of the primary benefits of flying a SE trajectory is to provide the crew with continuous Continental United States (CONUS) landing site access throughout the lunar month. Without a SE capability, the capsule must land either in water or at one of several distributed land sites in the Southern Hemisphere for a significant portion of a lunar month using a landing and recovery scenario similar to that employed during the Apollo program. With a SE trajectory, the capsule can land either in water at a site in proximity to CONUS or at one of several distributed landing sites within CONUS, thereby simplifying the operational requirements for crew retrieval and vehicle recovery, and possibly enabling a high degree of vehicle reusability. Note that a SE capability does not require that the vehicle land on land. A SE capability enables a longer-range flight than a direct-entry flight, which permits the vehicle to land at a much greater distance from the Entry Interface (EI) point. This does not exclude using this approach to push the landing point to a water location in proximity of CONUS and utilizing water or airborne recovery forces.

Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

Since 1994, adverse effects of transfusion transmitted to the French haemovigilance network are registered on "e-fit", the database of the French agency for the safety of health products (Afssaps). In order to improve their analysis, guidance supports have been made by Afssaps working groups. Each support deals with a blood transfusion side effect and is composed of five parts including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules of filing the notification form on e-fit. The major characteristics of sheets published or soon-to-be published are presented: transfusion-related acute lung injury, transfusion-transmitted bacterial infection, non-haemolytic febrile reaction, allergic reaction, transfusion-associated circulatory overload, hypotensive transfusion reaction, alloimmunization, erythrocyte incompatibility reaction and hemosiderosis. These new supports give relevant guidelines allowing a better analysis and evaluation of recipients' adverse reactions, particularly their diagnosis, gravity and accountability. They could also initiate studies in European and international haemovigilance and transfusion networks. PMID:21051267

Following de Broglie’s idea of a pilot wave, this paper treats quantum mechanics as a problem of stochastic optimal guidance law design. The guidance scenario considered in the quantum world is that an electron is the flight vehicle to be guided and its accompanying pilot wave is the guidance law to be designed so as to guide the electron to a random target driven by the Wiener process, while minimizing a cost-to-go function. After solving the stochastic optimal guidance problem by differential dynamic programming, we point out that the optimal pilot wave guiding the particle’s motion is just the wavefunction Ψ(t,x), a solution to the Schrödinger equation; meanwhile, the closed-loop guidance system forms a complex state–space dynamics for Ψ(t,x), from which quantum operators emerge naturally. Quantum trajectories under the action of the optimal guidance law are solved and their statistical distribution is shown to coincide with the prediction of the probability density function Ψ{sup ∗}Ψ. -- Highlights: •Treating quantum mechanics as a pursuit-evasion game. •Reveal an interesting analogy between guided flight motion and guided quantum motion. •Solve optimal quantum guidance problem by dynamic programming. •Gives a formal proof of de Broglie–Bohm’s idea of a pilot wave. •The optimal pilot wave is shown to be a wavefunction solved from Schrödinger equation.

Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. PMID:23024601

The science experiments for the Aeroassist Flight Experiment (AFE) will be greatly enhanced by taking measurements with no Reaction Control System (RCS) contamination just before perigee. Methods of modifying the AFE guidance to accomplish this are discussed. Several methods that could give up to 30 seconds of quiet time were investigated and the results of these guidance modifications shown. A 20 second quiet time is definitely possible and a 30 second quiet time may be possible if the guidance can be inactive past perigee. Some of the most significant being the criterion for determining if the mission is threatened. A limited follow-on test program is outlined.

Devising a strategy to deliver safe water to thousands of outlets spread across numerous buildings is always going to be a challenge, so how do you navigate your way through a bewildering labyrinth of sometimes contradictory guidance documents? Is there, in fact, simply too much guidance? Posing this question at a recent one-day conference on waterborne infections in healthcare facilities, Paul Nolan, authorised water engineer (AE), and operations manager for PFI provider, Lend Lease, took delegates through a review of the latest guidance and regulations, as Susan Pearson reports. PMID:25282983

Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

We are presenting a new optical encoder architecture for shaft encoding, both in incremental and absolute modes. This encoder is based on a diffractive optics technology platform. We have developed various disk based rotary diffractive encoders previously. This encoder is different in the way it is not a disk composed of successive gratings or computer generated holograms, but rather composed of a single element placed on the shaft. It is thus best suited for hollow shaft or end of shaft applications such as in encoder controlled electrical motors. This new architecture aims at solving some of the problems encountered with previous implementations of diffractive encoders such as disk wobble, disk to shaft centering and also encoding in harsh environments.

A travel guidance system is described for vehicles including: a heading sensor for detecting a direction of movement of a vehicle; a distance sensor for detecting a distance traveled by the vehicle; a map data storage medium preliminarily storing map data; a control unit for receiving a heading signal from the heading sensor and a distance signal from the distance sensor to successively compute a present position of the vehicle and for generating video signals corresponding to display data including map data from the map data storage medium and data of the present position; and a display having first and second display portions and responsive to the video signals from the control unit to display on the first display portion a map and a present portion mark, in which: the map data storage medium comprises means for preliminarily storing administrative division name data and landmark data; and the control unit comprises: landmark display means for: (1) determining a landmark closest to the present position, (2) causing a position of the landmark to be displayed on the map and (3) retrieving a landmark massage concerning the landmark from the storage medium to cause the display to display the landmark message on the second display portion; division name display means for retrieving the name of an administrative division to which the present position belongs from the storage medium and causing the display to display a division name message on the second display portion; and selection means for selectively actuating at least one of the landmark display means and the division name display means.

Driven by the need for new compounds to serve as biological probes and leads for therapeutic development and the growing accessibility of DNA technologies including high-throughput sequencing, many academic and industrial groups have begun to use DNA-encoded chemical libraries as a source of bioactive small molecules. In this review, we describe the technologies that have enabled the selection of compounds with desired activities from these libraries. These methods exploit the sensitivity of in vitro selection coupled with DNA amplification to overcome some of the limitations and costs associated with conventional screening methods. In addition, we highlight newer techniques with the potential to be applied to the high-throughput evaluation of DNA-encoded chemical libraries. PMID:25723146

Cyclic peptides can be highly valuable as bioactive molecules, both for biomedical applications and in basic research. We introduce a new fragment-based approach to access cyclic peptide structures in which one fragment is of synthetic origin and the other is genetically encoded. The synthetic peptide, which can contain one or more non-proteinogenic building blocks, is coupled to the recombinantly expressed peptide through two bonds, one formed by protein trans-splicing with a split intein and the other by oxime ligation. Semisynthetic macrocycles were obtained with high efficiency for various sequences and ring sizes; they can be prepared in quantities sufficient for initial bioactivity tests. We also prepared lipidated and d-amino-acid-containing peptides that were inspired by the peptide antibiotic daptomycin. Such structures are not accessible by other methods that harness the power of simple genetic diversification in the DNA-encoded part of the peptide. PMID:26691013

Streptococcus salivarius strains commonly produce bacteriocins as putative anti-competitor or signalling molecules. Here we report that bacteriocin production by the oral probiotic strain S. salivarius K12 is encoded by a large (ca. 190 kb) plasmid. Oral cavity transmission of the plasmid from strain K12 to a plasmid-negative variant of this bacterium was demonstrated in two subjects. Tests of additional S. salivarius strains showed large (up to ca. 220 kb) plasmids present in bacteriocin-producing isolates. Various combinations (up to 3 per plasmid) of loci encoding the known streptococcal lantibiotics salivaricin A, salivaricin B, streptin and SA-FF22 were localised to these plasmids. Since all bacteriocin-producing strains of S. salivarius tested to date appear to harbour plasmids, it appears that they may function as mobile repositories for bacteriocin loci, especially those of the lantibiotic class. PMID:16871420

The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.

This report describes techniques that provide increased jam resistance for digitized speech. Methods for increasing the jam resistance of pulse code modulated data are analyzed and evaluated in listener tests. Special emphasis is placed on new voice encoding approaches that take advantage of a spread spectrum system with a variable (or multiple)-data-rate/variable (or multiple)-AJ capability. Methods for matching a source to a channel in a jamming environment are investigated. Several techniques that provide about a 4 dB increase in jam resistance have been identified.

Producing a sentence involves encoding a preverbal message into a grammatical structure by retrieving lexical items and integrating them into a functional (semantic-to-grammatical) structure. Individuals with agrammatism are impaired in this grammatical encoding process. However, it is unclear what aspect of grammatical encoding is impaired and…

Two Reed Solomon error correcting encoders are presented. Schematic driven layout tools were used to create the encoder layouts. Special consideration had to be given to the architecture and logic to provide scalability of the encoder designs. Knowledge gained from these projects was used to create a more flexible schematic driven layout system.

...)); RUS Bulletin 1794A-601 provides guidance in preparing the ER for proposed actions which require EAs... (§ 1794.22(b)) and EAs (§ 1794.23(b)). A copy of this bulletin is available upon request by contacting...

...)); RUS Bulletin 1794A-601 provides guidance in preparing the ER for proposed actions which require EAs... (§ 1794.22(b)) and EAs (§ 1794.23(b)). A copy of this bulletin is available upon request by contacting...

...)); RUS Bulletin 1794A-601 provides guidance in preparing the ER for proposed actions which require EAs... (§ 1794.22(b)) and EAs (§ 1794.23(b)). A copy of this bulletin is available upon request by contacting...

...)); RUS Bulletin 1794A-601 provides guidance in preparing the ER for proposed actions which require EAs... (§ 1794.22(b)) and EAs (§ 1794.23(b)). A copy of this bulletin is available upon request by contacting...

The Delta inertial guidance system, part of the Delta launch vehicle improvement effort, has been flown on three launches and was found to perform as expected for a variety of mission profiles and vehicle configurations.

...: Norovirus Serological Reagents.'' This guidance document describes a means by which norovirus serological... by following the recommendations in the guidance document or by some other means that...

The Soil Screening Guidance is a tool that the U.S. Environmental Protection Agency (EPA) developed to help standardize and accelerate the evaluation and cleanup of contaminated soils at sites on the National Priorities List (NPL) with future residential land use. This guidance provides a methodology for environmental science/engineering professionals to calculate risk-based, site-specific, soil screening levels (SSLs) for contaminants in soil that may be used to identify areas needing further investigation at NPL sites.

Nerve guidance channels (NGCs) have been shown to facilitate regeneration after transection injury to the peripheral nerve or spinal cord. Various therapeutic molecules, including neurotrophic factors, have improved regeneration and functional recovery after injury when combined with NGCs; however, their impact has not been maximized partly due to the lack of an appropriate drug delivery system. To address this limitation, nerve growth factor (NGF) was incorporated into NGCs of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), P(HEMA-co-MMA). The NGCs were synthesized by a liquid-liquid centrifugal casting process and three different methods of protein incorporation were compared in terms of protein distribution and NGF release profile: (1) NGF was encapsulated (with BSA) in biodegradable poly(d,l-lactide-co-glycolide) 85/15 microspheres, which were combined with a PHEMA polymerization formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique; (2) pre-formed NGCs were imbibed with a solution of NGF/BSA and (3) NGF/BSA alone was combined with a PHEMA formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique. Using a fluorescently labelled model protein, the distribution of proteins in NGCs prepared with a coating of either protein-loaded microspheres or protein alone was found to be confined to the inner PHEMA layer. Sustained release of NGF was achieved from NGCs with either NGF-loaded microspheres or NGF alone incorporated into the inner layer, but not from channels imbibed with NGF. By day 28, NGCs with microspheres released a total of 220 pg NGF/cm of channel whereas those NGCs imbibed with NGF released 1040 pg/cm and those NGCs with NGF incorporated directly in a PHEMA layer released 8624 pg/cm. The release of NGF from NGCs with microspheres was limited by a slow-degrading microsphere formulation and by the maximum amount of microspheres that

Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.11008.001 PMID:26974341

After the first description of fertilization in flowering plants some 125 years ago (Strasburger E: Neue-Untersuchungen über den Befruchtungsvorgang bei den Phanerogamen als Grundlage für eine Theorie der Zeugung. Gustav Fischer; 1884), we are finally beginning to understand the various molecular mechanisms leading to sperm delivery and discharge inside the hidden micropylar region of the female gametophyte (embryo sac). The last phase of pollen tube guidance culminating in tube burst and explosive release of tube contents requires extensive crosstalk between both male and female gametophytes. The first molecules identified that play key roles in these processes represent highly polymorphic proteins, similar to major components of the plant innate immune system. Here we summarize recent advances and briefly discuss the underlying molecular mechanisms also in respect to prezygotic barriers of reproductive isolation. PMID:19896414

Turbo-code encoders are one of the spreadest family of error correcting codes used in the communication's world, especially in space transmissions. This paper presents an efficient technique to reconstruct turbo-code encoders which allows a passive adversary, with only few bits of an intercepted message encoded by the target turbocode encoder, to determine the parameters of the turbo-code encoder used, and therefore to decode online the communications. Thereby, our results confirm that keeping secret the parameters of turbo-code encoders can not be considered as a cryptographically way to ensure confidentiality. The starting point of our work is algorithms due to Filiol which enable to find the parameters of each convolutional encoder in the turbo-code encoder. Then, we recover the interleaver with two new algorithms, the first one based on the dynamic trie structure and the second one on a first order statistical test. The first algorithm is dedicated to noiseless channels. The asymptotic complexity of the complete process is O(n4) when a n2-bit message is available to attack a n-bit turbo-code encoder. The second algorithm works for every kind of channel and the noise does not matter much. Additionally, we present experimental results which underline the right detection threshold to use to recover the interleaver with a high probability. Furthermore, this method also works for turbo-code encoders composed of punctured convolutional encoders.

In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of {beta}-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct {beta}-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

Objective: To determine the accuracy of cone beam CT (CBCT) guidance and CT guidance in reaching small targets in relation to needle path complexity in a phantom. Methods: CBCT guidance combines three-dimensional CBCT imaging with fluoroscopy overlay and needle planning software to provide real-time needle guidance. The accuracy of needle positioning, quantified as deviation from a target, was assessed for inplane, angulated and double angulated needle paths. Four interventional radiologists reached four targets along the three paths using CBCT and CT guidance. Accuracies were compared between CBCT and CT for each needle path and between the three approaches within both modalities. The effect of user experience in CBCT guidance was also assessed. Results: Accuracies for CBCT were significantly better than CT for the double angulated needle path (2.2 vs 6.7 mm, p<0.001) for all radiologists. CBCT guidance showed no significant differences between the three approaches. For CT, deviations increased with increasing needle path complexity from 3.3 mm for the inplane placements to 4.4 mm (p=0.007) and 6.7 mm (p<0.001) for the angulated and double angulated CT-guided needle placements, respectively. For double angulated needle paths, experienced CBCT users showed consistently higher accuracies than trained users [1.8 mm (range 1.2–2.2) vs 3.3 mm (range 2.1–7.2) deviation from target, respectively; p=0.003]. Conclusion: In terms of accuracy, CBCT is the preferred modality, irrespective of the level of user experience, for more difficult guidance procedures requiring double angulated needle paths as in oncological interventions. Advances in knowledge: Accuracy of CBCT guidance has not been discussed before. CBCT guidance allows accurate needle placement irrespective of needle path complexity. For angulated and double-angulated needle paths, CBCT is more accurate than CT guidance. PMID:23913308

...Notice is hereby given that the EPA has posted its draft non- binding guidance titled, ``Guidance for 1-Hour SO2 NAAQS SIP Submissions'' on its Web site. The EPA invites public comments on this guidance document during the comment period specified below, and plans to issue an updated version of the guidance after reviewing timely submitted...

Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

"Earlier Guidance Opportunities (EGO): Priorities for the 1970's" was the topic for this Ohio Elementary Guidance Conference. In his keynote address entitled "New Perspectives on the Guidance of Younger Children - Can We Afford to Delay Vocational Guidance?" Dr. George E. Hill used EGO to say, "Education Gives Opportunity,""Ego's Grow on…

It is often thought that novelty benefits memory formation. However, support for this idea mostly comes from paradigms that are open to alternative explanations. In the present study we manipulated novelty in a word-learning task through task-irrelevant background images. These background images were either standard (presented repeatedly), or novel (presented only once). Two types of background images were used: Landscape pictures and fractals. EEG was also recorded during encoding. Contrary to the idea that novelty aids memory formation, memory performance was not affected by the novelty of the background. In the evoked response potentials, we found evidence of distracting effects of novelty: both the N1 and P3b components were smaller to words studied with novel backgrounds, and the amplitude of the N2b component correlated negatively with subsequent retrieval. We conclude that although evidence from other studies does suggest benefits on a longer time scale, novelty has no instantaneous benefits for learning. PMID:26005196

The disclosed encoder is adapted to produce both digital and analog output signals corresponding to the angular position of a rotary shaft, or the position of any other movable member. The digital signals comprise a series of binary signals constituting a multidigit code word which defines the angular position of the shaft with a degree of resolution which depends upon the number of digits in the code word. The basic binary signals are produced by photocells actuated by a series of binary tracks on a code disc or member. The analog signals are in the form of a series of ramp signals which are related in length to the least significant bit of the digital code word. The analog signals are derived from sine and cosine tracks on the code disc.

Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. PMID:26893348

The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. PMID:26893348

This paper examines the use of lidar wind measurements in the implementation of a guidance strategy for a nonlinear programming (NLP) launch guidance algorithm. The NLP algorithm uses B-spline command function representation for flexibility in the design of the guidance steering commands. Using this algorithm, the guidance system solves a two-point boundary value problem at each guidance update. The specification of different boundary value problems at each guidance update provides flexibility that can be used in the design of the guidance strategy. The algorithm can use lidar wind measurements for on pad guidance retargeting and for load limiting guidance steering commands. Examples presented in the paper use simulated wind updates to correct wind induced final orbit errors and to adjust the guidance steering commands to limit the product of the dynamic pressure and angle-of-attack for launch vehicle load alleviation.

The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules act...

...The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance entitled ``ANDAs: Stability Testing of Drug Substances and Products.'' FDA is recommending generic drug manufacturers follow the stability testing recommendations in the International Conference on Harmonisation (ICH) guidances Q1A (R2) through Q1E. The use of these ICH recommendations will......

In 2007 the International Association for Educational and Vocational Guidance (IAEVG) launched the Educational and Vocational Guidance Practitioner credential (EVGP) as one means of formally acknowledging the knowledge, skills, and personal attributes that practitioners need in order to provide quality career development services to clients. This…

A THEORY UPON WHICH ELEMENTARY GUIDANCE PROGRAMS CAN BE SOUNDLY DESIGNED IS PRESENTED. A MAJOR THEME IS THAT PSYCHOLOGICAL WELL-BEING OR GOOD ADJUSTMENT IS RELATED TO LEARNED, INDIVIDUAL COMPETENCIES SUCH AS COMMUNICATION AND INTERACTION IN DEPTH WITH OTHERS. THE APPROPRIATE CONCERN OF GUIDANCE THEN BECOMES TO FOSTER THESE COMPETENCIES, THUS…

Federal Guidance Report No. 14 provides federal facilities that use diagnostic and interventional x-ray equipment with updated recommendations for keeping doses as low as reasonably achievable without compromising the quality of patient care, This guidance is an update of Federal...

Papers from the sixteenth annual American Astronautical Society Rocky Mountain Guidance and Control Conference are presented. The topics covered include the following: advances in guidance, navigation, and control; control system videos; guidance, navigation and control embedded flight control systems; recent experiences; guidance and control storyboard displays; and applications of modern control, featuring the Hubble Space Telescope (HST) performance enhancement study.

Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

This document provides guidance for the implementation of the requirements identified in DOE-STD-6002-96, Safety of Magnetic Fusion Facilities: Requirements. This guidance is intended for the managers, designers, operators, and other personnel with safety responsibilities for facilities designated as magnetic fusion facilities. While the requirements in DOE-STD-6002-96 are generally applicable to a wide range of fusion facilities, this Standard, DOE-STD-6003-96, is concerned mainly with the implementation of those requirements in large facilities such as the International Thermonuclear Experimental Reactor (ITER). Using a risk-based prioritization, the concepts presented here may also be applied to other magnetic fusion facilities. This Standard is oriented toward regulation in the Department of Energy (DOE) environment as opposed to regulation by other regulatory agencies. As the need for guidance involving other types of fusion facilities or other regulatory environments emerges, additional guidance volumes should be prepared. The concepts, processes, and recommendations set forth here are for guidance only. They will contribute to safety at magnetic fusion facilities.

Three options have been developed for Fine Guidance Sensing (FGS) for coronagraphic observatories using a Fine Guidance Camera within a coronagraphic instrument. Coronagraphic observatories require very fine precision pointing in order to image faint objects at very small distances from a target star. The Fine Guidance Camera measures the direction to the target star. The first option, referred to as Spot, was to collect all of the light reflected from a coronagraph occulter onto a focal plane, producing an Airy-type point spread function (PSF). This would allow almost all of the starlight from the central star to be used for centroiding. The second approach, referred to as Punctured Disk, collects the light that bypasses a central obscuration, producing a PSF with a punctured central disk. The final approach, referred to as Lyot, collects light after passing through the occulter at the Lyot stop. The study includes generation of representative images for each option by the science team, followed by an engineering evaluation of a centroiding or a photometric algorithm for each option. After the alignment of the coronagraph to the fine guidance system, a "nulling" point on the FGS focal point is determined by calibration. This alignment is implemented by a fine alignment mechanism that is part of the fine guidance camera selection mirror. If the star images meet the modeling assumptions, and the star "centroid" can be driven to that nulling point, the contrast for the coronagraph will be maximized.

Previous research has indicated that use of guidance systems during endoscopy can improve the performance and decrease the skill variation of physicians. Current guidance systems, however, rely on computationally intensive registration techniques or costly and error-prone electromagnetic (E/M) registration techniques, neither of which fit seamlessly into the clinical workflow. We have previously proposed a real-time image-based registration technique that addresses both of these problems. We now propose a system-level approach that incorporates this technique into a complete paradigm for real-time image-based guidance in order to provide a physician with continuously-updated navigational and guidance information. At the core of the system is a novel strategy for guidance of endoscopy. Additional elements such as global surface rendering, local cross-sectional views, and pertinent distances are also incorporated into the system to provide additional utility to the physician. Phantom results were generated using bronchoscopy performed on a rapid prototype model of a human tracheobronchial airway tree. The system has also been tested in ongoing live human tests. Thus far, ten such tests, focused on bronchoscopic intervention of pulmonary patients, have been run successfully.

Image-guided interventions are an increasingly important part of clinical minimally invasive procedures. However, up to now they cannot be performed under 4D (3D + time) guidance due to the exceedingly high x-ray dose. In this work we investigate the applicability of compressed sensing reconstructions for highly undersampled CT datasets combined with the incorporation of prior images in order to yield low dose 4D intervention guidance. We present a new reconstruction scheme prior image dynamic interventional CT (PrIDICT) that accounts for specific image features in intervention guidance and compare it to PICCS and ASD-POCS. The optimal parameters for the dose per projection and the numbers of projections per reconstruction are determined in phantom simulations and measurements. In vivo experiments in six pigs are performed in a cone-beam CT; measured doses are compared to current gold-standard intervention guidance represented by a clinical fluoroscopy system. Phantom studies show maximum image quality for identical overall doses in the range of 14 to 21 projections per reconstruction. In vivo studies reveal that interventional materials can be followed in 4D visualization and that PrIDICT, compared to PICCS and ASD-POCS, shows superior reconstruction results and fewer artifacts in the periphery with dose in the order of biplane fluoroscopy. These results suggest that 4D intervention guidance can be realized with today’s flat detector and gantry systems using the herein presented reconstruction scheme.

The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ``Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1.

Alternative letdown guidance strategies are examined for landing of a VTOL aircraft onboard a small aviation ship under adverse environmental conditions. Off line computer simulation of shipboard landing task is utilized for assessing the relative merits of the proposed guidance schemes. The touchdown performance of a nominal constant rate of descent (CROD) letdown strategy serves as a benchmark for ranking the performance of the alternative letdown schemes. Analysis of ship motion time histories indicates the existence of an alternating sequence of quiescent and rough motions called lulls and swells. A real time algorithms lull/swell classification based upon ship motion pattern features is developed. The classification algorithm is used to command a go/no go signal to indicate the initiation and termination of an acceptable landing window. Simulation results show that such a go/no go pattern based letdown guidance strategy improves touchdown performance.

Control circuit designed for use with commercially available AHA4610 Reed-Solomon encoder. Needed to select depth of interleaving and to synchronize input and output blocks of data and parity bits with suitable clock signals. Circuit provides synchronizing and control signals for Reed-Solomon encoder. Encoder can operate with asynchronous input and output data streams at rates up to 80 Mb/s. Interleaving depth selectable, and accommodation to input data rate automatic.

It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can

To promote the education on medicines in school, guidance is, as a rule, to be given in the health education of the Subject, "Health and Physical Education" indicated as a curriculum standard in lower and upper secondary school, and in the health guidance, which carry out in Special Activities and Integrated Studies, etc. Guidance is mainly carried by the teacher for health and physical in health education and school nurse teacher (yogo teacher) in health guidance. In health education we have only limited school hours, and generally use the text book. Some teachers feel resistance to teach medicines because of needs on the special knowledge, however teachers should deal with medicines based on curriculum standard. School pharmacist is a member of school, and has a special knowledge for medicines, and he/she can support teachers as a provider of teaching materials, an adviser, and for a guest teacher. It is important for school pharmacist to understand the contents indicated in curriculum standard and to use glossary to be able to understand for children. In the guidance of health, it is not necessary to teach based on curriculum standard, and it can deal with advanced contents on medicines. However it is important to understand for children what are appropriate contents according to the development stage. To use the packages and instructions for medicines provided at home are good materials for children to have interest the medicines in their guidance. The objectives of education on medicines enable children to cultivate practical abilities for the maintenance and improvement of health. PMID:24292178

In this paper, we present two encoding methods for block-circulant LDPC codes. The first is an iterative encoding method based on the erasure decoding algorithm, and the computations required are well organized due to the block-circulant structure of the parity check matrix. The second method uses block-circulant generator matrices, and the encoders are very similar to those for recursive convolutional codes. Some encoders of the second type have been implemented in a small Field Programmable Gate Array (FPGA) and operate at 100 Msymbols/second.

Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

Since Epstein Barr virus was shown to encode microRNAs(miRNAs) in 2004, more than 470 miRNAs have been discovered in α-, β-, and γ-herpesviruses. MiRNAs are small non-coding RNA molecules and generally only have 18-25 nucleotides in length, which can regulate the expression of target genes by targeting its transcripts. Herpesvirus-encoded miRNAs not only target the key genes from latency to lytic replication, but also regulate various host cellular genes. Current data manifest that herpesvirus-encoded miRNAs can regulate viral latent infection and lytic replication, immune recognition, apoptosis, and tumorigenesis. The purpose of this paper is to summarize the targets and their fuction of hepesvirus-encoded miRNAs, in order to provide theoretical support for further analysis herpesviral pathogenesis. PMID:26951018

Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love. PMID:26178023

New fundamental interface sensor concepts were identified and investigated including tabulation of the physical and performance characteristics of two new interface detector concepts: - natural background radiation and magnetic spin resonance. Studies of guidance and control techniques for the longwall miner identified three basic systems for use in automated/remote controlled longwall mining. The following projects were initiated: system study which will more completely define the longwall guidance and control system design concepts; integration of the various control functions (vertical, yaw, and roll); and hardware technical requirements.

Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit in which the time delay inherent with communication will make remote guidance impractical. The Virtual Ultrasound Guidance system is a combination of hardware and software. The hardware portion includes, but is not limited to, video glasses that allow hands-free, full-screen viewing. The glasses also allow the operator a substantial field of view below the glasses to view and operate the ultrasound system. The software is a comprehensive video program designed to guide an inexperienced operator through a detailed ultrasound or echocardiographic study without extensive training or guidance from the ground. The program contains a detailed description using video and audio to demonstrate equipment controls, ergonomics of scanning, study protocol, and scanning guidance, including recovery from sub-optimal images. The components used in the initial validation of the system include an Apple iPod Classic third-generation as the video source, and Myvue video glasses. Initially, the program prompts the operator to power-up the ultrasound and position the patient. The operator would put on the video glasses and attach them to the video source. After turning on both devices and the ultrasound system, the audio-video guidance would then instruct on patient positioning and scanning techniques. A detailed scanning protocol follows with descriptions and reference video of each view along with

Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love. PMID:26178023

This paper examines ship motion pattern directed letdown guidance strategies for landing a VTOL aircraft onboard a small aviation ship under adverse environmental conditions. Off-line computer simulation of the shipboard landing task is utilized for assessing the relative merits of the proposed guidance schemes. A sum of seventy sinusoids representation is used to model the ship motion time histories. The touchdown performance of a nonimal constant-rate-of-descent (CROD) letdown strategy serves as a benchmark for ranking the performance of the alternative letdown schemes.

The Aeroassist Flight Experiment scheduled for the early 1990's will demonstrate the use of a low L/D lifting brake using aerodynamic drag to return a spacecraft from a high energy to a low earth orbit. The experimental vehicle will be deployed and retrieved by the Shuttle Orbiter. This paper reviews some of the challenges, problems, and solutions encountered to date during guidance system development, with emphasis on technology advances which will benefit an operational Orbit Transfer Vehicle (OTV). Key factors to be discussed include guidance alternatives, aerodynamic modeling, navigation requirements, the impact of atmospheric uncertainties, and flight profile alternatives considered during initial planning.

This article outlines the relative orbit control (guidance algorithm and its preliminary performance tests evaluation) that will be tested by the CNES Team on FFIORD (Formation Flying In Orbit Ranging Demonstration) onboard PRISMA mission. After a brief summary of the PRISMA mission context, the paper provides a full description of the rendezvous function involved in the approaching guidance experiment. This FFIORD onboard function is detailed in terms of on-board algorithmic method (basic algorithm and enhanced alternative), sensibility analysis used to construct maneuver plans and preliminary tests results.

In view of the variability of municipal sludge quality, appropriate procedures must be followed to collect and analyze samples that accurately represent each POTW's sludge quality. The manual was developed to provide that guidance to POTW operators, engineers, managers, chemists and permit writers. It was intended to provide guidance in developing and implementing a sampling and analysis program, to gather information on sludge quality and determine compliance with permit conditions. The manual is based on current, state-of-the-art field and laboratory practices and therefore is recommended for all sludge sampling and analysis programs.

A reduced-order method employing decomposition, based on time-scale separation, of the 4-D state space in a 2-D slow manifold and a family of 2-D fast manifolds is shown to provide an excellent approximation to the full-order minimum-fuel ascent trajectory. Near-optimal guidance is obtained by tracking the reduced-order trajectory. The tracking problem is solved as regulation problems on the family of fast manifolds, using the exact linearization methodology from nonlinear geometric control theory. The validity of the overall guidance approach is indicated by simulation.

The formulation of a general nonlinear programming guidance algorithm that incorporates wind measurements in the computation of ascent guidance steering commands is discussed. A nonlinear programming (NLP) algorithm that is designed to solve a very general problem has the potential to address the diversity demanded by future launch systems. Using B-splines for the command functional form allows the NLP algorithm to adjust the shape of the command profile to achieve optimal performance. The algorithm flexibility is demonstrated by simulation of ascent with dynamic loading constraints through a set of random wind profiles with and without wind sensing capability.

Fibronectin mediates myoblast-substratum attachment; one region of the molecule binds directly to the cell surface, while others bind to collagen, glycosaminoglycans, and other fibronectin molecules. There is evidence to suggest that fibronectin-containing extracellular matrices guide cell migration in vivo. We describe a method for producing regular deposits of fibronectin in vitro that can serve as a model system for studying cell-substrate interactions, cell orientation, and contact guidance. The novel culture substrate is prepared by allowing an aqueous solution of fibronectin and urea to dry in a culture dish and then washing away the urea crystals. Myogenic cells in vitro adhere to, align with, and migrate along, parallel streaks of fibronectin. This leads to the formation of myotubes that are long and thin, with little branching. Myogenic clones are highly elongated in the direction of the deposits, in contrast with the roughly circular clones seen in conventional cultures. Fibroblasts and limb bud mesenchymal cells align with fibronectin deposits, assuming a bipolar shape. PMID:6825944

Ultracold polar molecules in the quantum degenerate regime open the possibility of realizing quantum gases with long-range, and spatially anisotropic, interparticle interactions. Currently, we can create a gas of ultracold fermionic ground-state KRb molecules in with a peak density of 1012 cm-3 and a temperature just 1.4 times the Fermi temperature. We will report on efforts to further cool this gas of molecules. One possibility is to evaporatively cool a spin-polarized molecular Fermi gas confined in quasi-2D, where we would rely on dipole-dipole interactions for rethermalization. We acknowledge funding from NIST, NSF, and AFOSR-MURI.

In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson's spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson’s spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson’s spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

In picture quality assessment, the amount of distortion perceived by a human observer differs from one region to another according to its particular local content. This subjective perception can be explained/predicted by considering some simple psychovisual properties (masking) of the Human Visual System (HVS). We have implemented a HVS model based on a pyramid decomposition for extracting the spatial frequencies, associated with a multi-resolution motion representation. Then the visibility of the decoded errors is computed by exploiting the Kelly's contrast sensitivity spatio-velocity model. The resulting data is called a 'Quality-map.' Special attention has been paid to temporal/moving effects since, in the case of video sequences, motion strongly influences the subjective quality assessment. The quality of the motion information is thus preponderant. In the second part, two possible uses of these psychovisual properties for improving MPEG video encoding performances are depicted: (1) The pre-processing of the pictures to remove non-visible information using a motion adapted filtering. This process is efficient in term of bits saved and degradation is not significant especially on consumer electronic TV sets. (2) A perceptual quantizer based on a local adaptation scheme in order to obtain Quality-maps as uniform as possible (homogeneous perceived distortion), at constant bit-rate. Further improvements have been considered, especially when the viewer is tracking a moving object in the scene.

Aging characteristics and life expectancies of flight quality, tungsten filament, encoder lamps are similar to those of 'commercial' grade gas filled lamps of similar construction, filament material and filament temperature. The aging and final failure by filament burnout are caused by single crystal growth over large portions of the filament with the concomitant development of facets and notches resulting in reduction of cross section and mechanical weakening of the filament. The life expectancy of presently produced lamps is about one year at their nominal operating voltage of five volts dc. At 4.5 volts, it is about two years. These life times are considerably shorter, and the degradation rates of lamp current and light flux are considerably higher, than were observed in the laboratory and in orbit on lamps of the same type manufactured more than a decade ago. It is speculated that the filaments of these earlier lamps contained a crystallization retarding dopant, possibly thorium oxide. To obtain the desired life expectancy of or = to four years in present lamps, operating voltages of or = to four volts dc would be required.

Physical guidance is a strategy commonly used for noncompliance. In two experiments, we evaluated reinforcing effects of physical guidance. Experiment 1 include three individuals with developmental disabilities who were noncompliant with tasks. Anecdotal observations indicated physical contact was highly reinforcing, and a functional analysis identified attention as a reinforcer for problem behavior. Two conditions compared physical guidance following noncompliance and no physical guidance following noncompliance. Results showed noncompliance increased for all three participants when physical guidance followed noncompliance. The second experiment empirically evaluated the function of noncompliance prior to examining the effect of physical guidance on noncompliance. A functional analysis, conducted with two participants, indicated noncompliance served an escape function for one and an attention function for the other. Comparisons of physical guidance and no physical guidance indicated physical guidance resulted in decreased noncompliance for the participant with an escape function but increased noncompliance for the participant with an attention function. PMID:12205825

Over the past decade fMRI researchers have developed increasingly sensitive techniques for analyzing the information represented in BOLD activity. The most popular of these techniques is linear classification, a simple technique for decoding information about experimental stimuli or tasks from patterns of activity across an array of voxels. A more recent development is the voxel-based encoding model, which describes the information about the stimulus or task that is represented in the activity of single voxels. Encoding and decoding are complementary operations: encoding uses stimuli to predict activity while decoding uses activity to predict information about stimuli. However, in practice these two operations are often confused, and their respective strengths and weaknesses have not been made clear. Here we use the concept of a linearizing feature space to clarify the relationship between encoding and decoding. We show that encoding and decoding operations can both be used to investigate some of the most common questions about how information is represented in the brain. However, focusing on encoding models offers two important advantages over decoding. First, an encoding model can in principle provide a complete functional description of a region of interest, while a decoding model can provide only a partial description. Second, while it is straightforward to derive an optimal decoding model from an encoding model it is much more difficult to derive an encoding model from a decoding model. We propose a systematic modeling approach that begins by estimating an encoding model for every voxel in a scan and ends by using the estimated encoding models to perform decoding. PMID:20691790

Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

The primary guidance, navigation, and control systems for both the lunar module and the command module are described. Development of the Apollo primary guidance systems is traced from adaptation of the Polaris Mark II system through evolution from Block I to Block II configurations; the discussion includes design concepts used, test and qualification programs performed, and major problems encountered. The major subsystems (inertial, computer, and optical) are covered. Separate sections on the inertial components (gyroscopes and accelerometers) are presented because these components represent a major contribution to the success of the primary guidance, navigation, and control system.

Polyatomic molecule vibrations are analyzed as harmonic vibrations along normal coordinates. The energy eigenvalues are found for linear and nonlinear symmetric triatomic molecules for valence bond models of the potential function with arbitrary coupling coefficients; such models can usually be fitted to observed energy levels with reasonably good accuracy. Approximate normal coordinates for the H2O molecule are discussed. Degenerate vibrational modes such as occur in CO2 are analyzed and expressions for Fermi resonance between close-lying states of the same symmetry are developed. The bending modes of linear triatomic molecules are expressed in terms of Laguerre polynomials in cylindrical coordinates as well as in terms of Hermite polynomials in Cartesian coordinates. The effects of large-amplitude bending such as occur in the C3 molecule are analyzed, along with anharmonic effects, which split the usually degenerate bending mode energy levels. Finally, the vibrational frequencies, degeneracies, and symmetry properties of XY3, X2Y2, and XY4 type molecules are discussed.

Seven observations made by a career education team (a counselor, an occupational specialist, and classroom teachers) provided the basis for establishing career guidance goals. The goals were devoloped around the accepted elements of career education and implemented in a teacher-counselor shared accountability effort in Florida's Pinellas County.…

This guidance presents EPA`s site inspection (SI) strategy. The strategy discusses procedural guidelines to investigate potential Superfund (CERCLA) sites for evaluation pursuant to the Hazard Ranking System (HRS), revised in accordance with the Superfund Amendments and Reauthorization Act of 1986. The HRS is the primary means by which EPA evaluates sites for superfund`s National Priorities List (NPL).

The manual suggests various uses the guidance counselor can make of the Kuder interest surveys. Written by a counselor, the guide presents suggestions that reflect considerable experience with the Kuder tests. Guidelines for introducing, administering, and interpreting the instrument are included along with suggestions for ways to involve the…

A bibliography of materials relevant to the competency-based guidance curriculum of the North Carolina State Department of Public Instruction is presented in this document. Books for students, books for teacher/counselor use, filmstrips (sound), and videocassettes are listed. Grade ranges are provided for each item, although use of the materials…

Progress reports on guidance and attitude control mechanisms of different flight vehicles are presented. The vehicles considered include orbiting spacecraft, supersonic aircraft, and general aviation aircraft. Data also cover orbital transfer using low thrust, automatic landing logic for aircraft, optimal and three dimensional turns for supersonic aircraft, and orbital rendezvous.

This competency-based curriculum for prevocational exploration in West Virginia provides experiences at grades 9 and 10 related to exploring careers and educational programs for those careers. The guidance units are designed to assist the counselor in providing activities that relate to ongoing hands-on activities in prevocational business,…

This review of guidance and counseling research includes reports of hypothesis testing based on hard data and behavioral analysis designs, reports of surveys and evaluations, and comments and recommenda- tions from reflections on experience and survey findings. The materials, originating from New Zealand between 1970 and 1979, are classified on…

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research...

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research...

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research...

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research...

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Miscellaneous Provisions § 314.445 Guidance... comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research...

While opinions from the general public are certainly important, opinions from the museum staff are also necessary to improve user service systems. this article introduces two groups of museum staff who have evaluated the usability of mobile guidance systems in Japanese museums. One group is the research team who used the PDA system in the National…

The Gamma Guidance Algorithm which controls the inertial upper stage is described. The results of an independent assessment of the algorithm's performance in satisfying the NASA missions' targeting objectives are presented. The results of a launch window analysis for a Galileo mission, and suggested improvements are included.

The kinds of vocational guidance available to women from 1910 to 1940 are discussed in this paper. As the number of women college graduates increased in the 1890s and especially in the first decade of the 20th century, concern also grew for what all these trained women would do to earn a living after they graduated and before they married (if they…

The purpose of this study is to determine the guidance and counseling needs of middle school (i.e., sixth, seventh, and eighth grades) students from their points of views by using qualitative research techniques. In addition, while collecting the data, semi-structured interview technique is used as a method of data collection. The study was…

This book deals not with the administrative or information searching processes related to the guidance function of providing occupational information, but with the substantive information itself. It presents a contemporary view of values, trends, and principles, derived primarily from statistical information describing the current world of work.…

THE PURPOSE WAS TO IDENTIFY ABLE STUDENTS FROM DISADVANTAGED URBAN AREAS AND TO STIMULATE THEM THROUGH CULTURAL EXPERIENCES, SPECIAL CLASSES, AND GUIDANCE TO SEEK HIGHER EDUCATIONAL AND VOCATIONAL GOALS. A PRIMARY OBJECTIVE WAS TO REFINE THE METHODS AND TECHNIQUES FOR PREDICTION OF ACADEMIC POTENTIAL, THROUGH APTITUDE TESTING, ACHIEVEMENT TESTING,…

A Singular perturbation guidance law has been developed for medium-range surface-to-air missiles. This guidance law is a significant extension of a previously developed guidance law for short-range missiles; in medium-range intercepts, the problem of energy management should be addressed in addition to homing guidance. The mathematical formulation has been simplified by introducing separation of time scales. Target Trajectory Estimation: A recursive algorithm for estimation of autoregressive moving average (ARMA) model parameters from noisy samples has been developed. Application of this algorithm to parameter estimation problems has exhibited its fast convergence and unbiasedness in the presence of noise, even with short data records. The algorithm has two versions, a Recursive Maximum Likelihood (RML) form and a Recursive Prediction Error (RPE) form, both of which possess a parallel structure that makes them highly suitable for parallel-processing implementation. Adaptive autopilots: Lattice-form algorithms have been developed for fast, recursive identification and control of time-varying systems. These algorithms have excellent numerical properties and a modular structure that makes them suitable for on-board real-time implementation.

The Organization for Economic Co-operation and Development, the World Bank, and the European Commission have conducted reviews of the career guidance policies and practices in 37 countries. The 37 country studies, together with the 3 synthesis reports and a number of other commissioned papers, constitute the largest database on career guidance…

Materials contained in this career guidance unit are designed to develop in five-and six-year-old children an awareness of their senses and the related body organs, likenesses and differences, and self-control. The nineteen activities included in the unit vary in length from twenty to sixty minutes; the entire unit requires approximately ten hours…

This report presents a summary of work done to determine the inherent angular accuracy achievable with the guidance and control precision standoff guidance antenna. The antenna is a critical element in the anti-jam single station guidance program since its characteristics can limit the intrinsic location guidance accuracy. It was important to determine the extent to which high ratio beamsplitting results could be achieved repeatedly and what issues were involved with calibrating the antenna. The antenna accuracy has been found to be on the order of 0.006 deg. through the use of a straightforward lookup table concept. This corresponds to a cross range error of 21 m at a range of 200 km. This figure includes both pointing errors and off-axis estimation errors. It was found that the antenna off-boresight calibration is adequately represented by a straight line for each position plus a lookup table for pointing errors relative to broadside. In the event recalibration is required, it was found that only 1% of the model would need to be corrected.

This article is based on a keynote presentation at an international conference where the focus was cross-over career guidance. Simon and Garfunkel's popular song, "Bridge over troubled water", was used as a metaphor for exploring the cross-over theme. Some of the concepts under consideration included the working alliance, the importance of a…

The use of atmospheric drag for slowing satellite in high energy, high apogee orbits to a lower energy, lower apogee orbit about the Earth is investigated. The high energy orbit is assumed to intercept the Earth's atmosphere. Guidance for the atmospheric phase of the trajectory may be done using the aerodynamic forces generated by the passage through the atmosphere. This research was concerned with the investigation of several methods of guidance during the atmospheric phase to cause a significant reduction in the final velocity as the vehicle leaves the atmosphere. In addition, the velocity direction was controlled to exit to a desired target orbit. Lastly excess aerodynamic lift was used to effect a plane change between the entry orbit plane and the exit orbit plane to achieve a desired orbit plane. The guidance methods were applied to a 3 degree-of-freedom simulation which included an oblate Earth gravity model and a rotating atmosphere. Simulation results were compared on the basis of speed of computation of the guidance parameters and amount of added velocity necessary to achieve the desired orbit.

Developments of the linear quadratic optimal control problem are discussed. The theory is applicable to the development of neighboring optimal feedback guidance gains, and is useful as a tool for synthesizing feedback control laws. A computer program which requires only the pertinent matrices of the linear quadratic problem is described.

The directive provides guidance on the use of premium payments in CERCLA settlements. It describes the key features of a premium payment settlement, considerations regarding timing of the settlement, and the factors to be considered in deciding if a premium should be accepted.

Outcomes of guidance can be assessed at these three levels: individual, where they are immediate; organizational, where they are intermediate; or societal, where they are ultimate. They may result in learning outcomes, school effectiveness, economic benefits, or social benefits. Various designs of outcome evaluation are described and…

A document from the U.S. Department of Education intended to clarify schools' responsibility to make sure students with disabilities have access to extracurricular sports has drawn sharply different opinions. Disability-rights advocates welcome the guidance, while critics say federal officials are pushing requirements that could place new…

In this article the authors argue for the importance of narrative-based approaches in career guidance work in an uncertain, unpredictable world. This requires a paradigmatic shift in thinking that can be too difficult, at present, for some practitioners. The article reports on the first phase of a collaborative project with a group of…

The counseling staff at a suburban, comprehensive, four-year high school in southern California developed and implemented a Career Guidance program for grades nine through twelve. With assistance and cooperation from teachers, students participated in exploration of vocational interests, personal values, and individual aptitudes in Grades 9 and…

This document offers guidance to schools on how assessment can support enterprise education. It presents the interim findings from research carried out by the National Foundation for Educational Research (NFER) for the Department for Education and Skills (DfES) in secondary schools in England. Enterprise capability is the key outcome of enterprise…

Finds the Sampson et al. guidelines for computer-assisted career guidance systems (CE 521 972) comprehensive and self-explanatory, but states that user judgment is still required. Suggests revision of existing standards to take into account the feature-cost analysis method. (SK)

Investigated students' perceptions of the primary compulsory segment of the career guidance program offered by Swift Current Comprehensive High School. Students reported positive perceptions of the total program and of counselor assistance, particularly of the CHOICES component of the program, with mixed perceptions of the Strong-Campbell Interest…

A flight qualified laser radar called LAMP (LAser MaPper) is under development at JPL. LAMP is a guidance and control sensor that can form 3 dimensional images of its field of regard. This paper describes the detailed design of the LAMP sensor.

Image guidance is one of the major challenges common to all minimally invasive procedures including biopsy, thermal ablation, endoscopy, and laparoscopy. This is essential for (1) identifying the target lesion, (2) planning the minimally invasive approach, and (3) monitoring the therapy as it progresses. MRI is an ideal imaging modality for this purpose, providing high soft tissue contrast and multiplanar imaging, capability with no ionizing radiation. An interventional/surgical MRI suite has been developed at Brigham and Women's Hospital which provides multiplanar imaging guidance during surgery, biopsy, and thermal ablation procedures. The 0.5T MRI system (General Electric Signa SP) features open vertical access, allowing intraoperative imaging to be performed. An integrated navigational system permits near real-time control of imaging planes, and provides interactive guidance for positioning various diagnostic and therapeutic probes. MR imaging can also be used to monitor cryotherapy as well as high temperature thermal ablation procedures sing RF, laser, microwave, or focused ultrasound. Design features of the interventional MRI system will be discussed, and techniques will be described for interactive image acquisition and tracking of interventional instruments. Applications for interactive and near-real-time imaging will be presented as well as examples of specific procedures performed using MRI guidance.

This document discusses the role of the guidance counselor in helping with the academic achievement of students. One way to do this is to instruct teachers and principals in some of the basic tenets from educational psychology that can help students feel more positive about themselves. Being unable to meet high curricular standards often leads to…

The mnemonic consequences of semantic, acoustic, and orthographic encoding and the relationships between encoding and retrieval cues were investigated in an incidental-learning experiment involving 24 first-, third-, and fifth-grade pupils. Each child was asked one orienting question for each of 18 words; the questions differed in the type of…

... for either manual or automatic operation. (2) Inputs. The encoder shall have two inputs, one for audio... encoder shall have two outputs, one audio port and one data port (RS-232C with standard protocol and 1200... frequency components outside 200 to 4000 Hz shall be attenuated by 40 dB or more with respect to the...

Image storage requirements for several encoding methods are investigated and the use of quadtrees with multigray level or multicolor images are explored. The results of encoding a variety of images having up to 256 gray levels using three schemes (full raster, runlength and quadtree) are presented. Although there is considerable literature on the use of quadtrees to store and manipulate binary images, their application to multilevel images is relatively undeveloped. The potential advantage of quadtree encoding is that an entire area with a uniform gray level may be encoded as a unit. A pointerless quadtree encoding scheme is described. Data are presented on the size of the quadtree required to encode selected images and on the relative storage requirements of the three encoding schemes. A segmentation scheme based on the statistical variation of gray levels within a quadtree quadrant is described. This parametric scheme may be used to control the storage required by an encoded image and to preprocess a scene for feature identification. Several sets of black and white and pseudocolor images obtained by varying the segmentation parameter are shown.

We experimentally demonstrate an information encoding protocol using the two degrees of freedom of Laguerre Gaussian modes having different radial and azimuthal components. A novel method, based on digital holography, for information encoding and decoding using different data transmission scenarios is presented. The effects of the atmospheric turbulence introduced in free space communication is discussed as well.

This article presents several empirical studies of syntactically encoded evidentiality in English. The first part of our study consists of an adult online experiment that confirms claims in Asudeh & Toivonen (2012) that raised Perception Verb Similatives (PVSs; e.g. "John looks like he is sick") encode direct evidentiality. We then…

In order to advance entry guidance technology two different research areas have been explored with the objective of increasing the reachable landing area and the landing accuracy for future Mars missions. Currently only the northern hemisphere of Mars is available for landing due to its low elevation. Only low elevation landing sites have the necessary atmospheric density to allow landing using current Entry, Descent and Landing (EDL) technology. In order to reach most of the Ancient Highlands, the majority of the southern hemisphere, advanced EDL technology is needed in multiple fields, including entry guidance. The first research area is the definition and applications of reachable and controllable sets for entry. The definition of the reachable and controllable sets provides a framework for the study of the capabilities of an entry vehicle in a given planet. Reachable and controllable sets can be used to comprehensively characterize the envelope of trajectories that a vehicle can fly, the sites it can reach and the entry states that can be accommodated. The sets can also be used for the evaluation of trajectory planning algorithms and to assist in the selection of the entry or landing sites. In essence, the reachable and controllable sets offer a powerful vehicle and trajectory analysis and design framework that allows for better mission design choices. In order to illustrate the use of the sets, they are computed for a representative Mars mission using two different vehicle configurations. The sets characterize the impact of the vehicle configuration on the entry capability. Furthermore, the sets are used to find the best skip-entry trajectory for a return from the Moon mission, highlighting the utility of the sets in atmospheric maneuvers other than entry. The second research area is the development of the components of an entry guidance algorithm that allow high elevation landing and provide as well high landing accuracy. The approach taken follows the

The development of the microprocessor and mini-computer for industrial process control has made the optical shaft angle encoder a natural choice for a position feedback transducer. Many of these applications, however, require the encoder to operate reliably in extremely hostile environments. In response to this, the encoder manufacturer has been faced with reliability problems which fall into the following general categories: 1. Exposure to weather 2. Wide operating and storage temperature range 3. Exposure to corrosive chemicals 4. Severe shock and vibration 5. High electrical noise levels 6. Severe blows to encoder housing 7. Operation in explosive atmospheres Three of these applications expose the encoder to most of these environmental conditions: 1. A jack-up control position feedback for an offshore oil well drilling rig 2. A depth measurement system for oil well logging instrumentation 3. Elevation and azimuth feedback for a solar power plant heliostat

While there is theoretical evidence that positrons can bind to atoms, calculations for molecules are much less precise. Unfortunately, there have been no measurements of positron-atom binding, due primarily to the difficulty in forming positron-atom bound states in two-body collisions. In contrast, positrons attach to molecules via Feshbach resonances (VFR) in which a vibrational mode absorbs the excess energy. Using a high-resolution positron beam, this VFR process has been studied to measure binding energies for more than 40 molecules. New measurements will be described in two areas: positron binding to relatively simple molecules, for which theoretical calculations appear to be possible; and positron binding to molecules with large permanent dipole moments, which can be compared to analogous, weakly bound electron-molecule (negative-ion) states. Binding energies range from 75 meV for CS2 (no dipole moment) to 180 meV for acetonitrile (CH3CN). Other species studied include aldehydes and ketones, which have permanent dipole moments in the range 2.5 - 3.0 debye. The measured binding energies are surprisingly large (by a factor of 10 to 100) compared to those for the analogous negative ions, and these differences will be discussed. New theoretical calculations for positron-molecule binding are in progress, and a recent result for acetonitrile will be discussed. This ability to compare theory and experiment represents a significant step in attempts to understand positron binding to matter. In collaboration with A. C. L. Jones, J. J. Gosselin, and C. M. Surko, and supported by NSF grant PHY 07-55809.

For the last 15 years, there has been an explosion in the development of genetically-encoded biosensors that report enzyme activity, chemical transformation, or concentration of ions and molecules in living cells. Now, there are well over 120 biosensors of different cellular targets. As a general design principle, these sensors convert a molecular event, such as the binding of a molecule to a sensing domain or a signal-induced change in protein conformation, into a change in the sensors’ fluorescence properties. In contrast to small-molecule sensors, genetically-encoded sensors are generated as cells, tissues, or organisms translate sensor-encoding nucleic acid sequences, which have been introduced by transgenic technologies. One of the best developed classes of biosensors is that of genetically-encoded Ca2+ indicators (GECIs). Here, we briefly summarize the properties of ratiometric GECIs that permit them to be used to quantify Ca2+ in specific cellular locations, such as the cytosol, nucleus, endoplasmic reticulum, and mitochondria. We also provide two protocols that describe in detail how to carry out such quantitative measurements in cultured mammalian cells. PMID:25561625

The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton–matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem. PMID:26283918

Guidance behavior generated either by artificial agents or humans has been actively studied in the fields of both robotics and cognitive science. The goals of these two fields are different. The former is the automatic generation of appropriate or even optimal behavior, while the latter is the understanding of the underlying mechanism. Their challenges, though, are closely related, the most important one being the lack of a unified, formal and grounded framework where the guidance behavior can be modeled and studied. This dissertation presents such a framework. In this framework, guidance behavior is analyzed as the closed-loop dynamics of the whole agent-environment system. The resulting dynamics give rise to interaction patterns. The central points of this dissertation are that: first of all, these patterns, which can be explained in terms of symmetries that are inherent to the guidance behavior, provide building blocks for the organization of behavior; second, the existence of these patterns and humans' organization of their guidance behavior based on these patterns are the reasons that humans can generate successful behavior in spite of all the complexities involved in the planning and control. This dissertation first gives an overview of the challenges existing in both scientific endeavors, such as human and animal spatial behavior study, and engineering endeavors, such as autonomous guidance system design. It then lays out the foundation for our formal framework, which states that guidance behavior should be interpreted as the collection of the closed-loop dynamics resulting from the agent's interaction with the environment. The following, illustrated by examples of three different UAVs, shows that the study of the closed-loop dynamics should not be done without the consideration of vehicle dynamics, as is the common practice in some of the studies in both autonomous guidance and human behavior analysis. The framework, the core concepts of which are

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein. PMID:26005528

…once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. Santiago Ramón y Cajal Cajal's neurotropic theory postulates that the complexity of the nervous system arises from the collaboration of neurotropic signals from neuronal and non-neuronal cells and that once development has ended, a paucity of neurotropic signals means that the pathways of the central nervous system are "fixed, ended, immutable". While the capacity for regeneration and plasticity of the central nervous system may not be quite as paltry as Cajal proposed, regeneration is severely limited in scope as there is no spontaneous regeneration of long-distance projections in mammals and therefore limited opportunity for functional recovery following spinal cord injury. It is not a far stretch from Cajal to hypothesize that reappropriation of the neurotropic programs of development may be an appropriate strategy for reconstitution of injured circuits. It has become clear, however, that a significant number of the molecular cues governing circuit development become re-active after injury and many assume roles that paradoxically obstruct the functional re-wiring of severed neural connections. Therefore, the problem to address is how individual neural circuits respond to specific molecular cues following injury, and what strategies will be necessary for instigating functional repair or remodeling of the injured spinal cord. PMID:26676670

The successful production of a dense sample of ultracold ground state KRb polar molecules [1] opens the door to a new era of research with dipolar gases and lattices of such species. This feat was achieved by first associating a K and a Rb atom to make a weakly bound Feshbach molecule and then coherently transferring the population to the ground vibrational level of the molecule. This talk focuses on theoretical issues associated with making and using ultracold polar molecules, using KRb as an example [2]. Full understanding of this species and the processes by which it is made requires taking advantage of accurate molecular potentials [3], ab initio calculations [4], and the properties of the long-range potential. A highly accurate model is available for KRb for all bound states below the ground state separated atom limit and could be constructed for other species. The next step is to develop an understanding of the interactions between polar molecules, and their control in the ultracold domain. Understanding long-range interactions and threshold resonances will be crucial for future work. [1] K.-K. Ni, et al, Science 322, 231(2008). [2] P. S. Julienne, arXiv:0812:1233. [3] Pashov et al., Phys. Rev. A76, 022511 (2007). [4] S. Kotochigova, et al., arXiv:0901.1486.

... Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This article ... should patients with immune deficiency be given the vaccine? Immune deficient patients have a decreased resistance to ...

The Technical Guidance for Assessing Environmental Justice in Regulatory Analysis (also referred to as the Environmental Justice Technical Guidance or EJTG) is intended for use by Agency analysts, including risk assessors, economists, and other analytic staff that conduct analyse...

The Implementation Guidance for Ambient Water Quality Criteria for Bacteria is a guidance document to assist state, territory, and authorized tribal water quality programs in adopting and implementing bacteriological water quality criteria into their water quality standards to pr...

The ozone hole that forms in the spring months over the Antarctic is thought to be produced through a network of chemical reactions catalyzed by the surfaces of ice crystals in polar stratospheric clouds (PSCs). A reaction between chlorine reservoir molecules, such as HCl + ClONO{sub 2} > HNO{sub 3} + Cl{sub 2}, is kinetically forbidden in the gas phase but proceeds quickly on the surface of ice and produces Cl{sub 2} molecules that are photodissociated by sunlight to yield the Cl atoms that destroy ozone. This destructive chain of events begins when HCl molecules stick to the ice crystals, and the mechanism for this crucial sticking process has been the subject of much debate. Recent work describes a mechanism that explains how HCl sticks to ice. This article goes on to detail research focusing surface reactions in stratospheric chemistry. 9 refs., 1 fig.

Recent theoretical studies on positronium ions and molecules are discussed. A positronium ion is a three particle system consisting of two electrons in singlet spin state, and a positron. Recent studies include calculations of its binding energy, positron annihilation rate, and investigations of its doubly excited resonant states. A positronium molecule is a four body system consisting of two positrons and two electrons in an overall singlet spin state. The recent calculations of its binding energy against the dissociation into two positronium atoms, and studies of auto-detaching states in positronium molecules are discussed. These auto-dissociating states, which are believed to be part of the Rydberg series as a result of a positron attaching to a negatively charged positronium ion, Ps-, would appear as resonances in Ps-Ps scattering.

A graph theoretic measure of extended atomic branching is defined that accounts for the effects of all atoms in the molecule, giving higher weight to the nearest neighbors. It is based on the counting of all substructures in which an atom takes part in a molecule. We prove a theorem that permits the exact calculation of this measure based on the eigenvalues and eigenvectors of the adjacency matrix of the graph representing a molecule. The definition of this measure within the context of the Hückel molecular orbital (HMO) and its calculation for benzenoid hydrocarbons are also studied. We show that the extended atomic branching can be defined using any real symmetric matrix, as well as any Hermitian (self-adjoint) matrix, which permits its calculation in topological, geometrical, and quantum chemical contexts.

Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

Experimental techniques that interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. In this study, we review several technologies that can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

The photochemistry of two diatomic and eight polyatomic molecules is discussed quantitatively. For an interstellar molecule, the lifetime against photodecomposition depends upon the absorption cross section, the quantum yield or probability of dissociation following photon absorption, and the interstellar radiation field. The constant energy density of Habing is used for the unobserved regions of interstellar radiation field, and the field in obscuring clouds is estimated by combining the constant flux with the observed interstellar extinction curve covering the visible and ultraviolet regions. Lifetimes against photodecomposition in the unobscured regions and as a function of increasing optical thickness in obscuring clouds are calculated for the ten species. The results show that, except for CO, all the molecules have comparable lifetimes of less than one hundred years. Thus they can exist only in dense clouds and can never have been exposed to the unobscured radiation. The calculations further show that the lifetimes in clouds of moderate opacity are of the order of one million years.

We report the detection toward η Carinae of six new molecules, CO, CN, HCO+, HCN, HNC, and N2H+, and of two of their less abundant isotopic counterparts, 13CO and H13CN. The line profiles are moderately broad (~100 km s-1), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO+ do not appear to be underabundant in η Carinae. On the other hand, molecules containing nitrogen or the 13C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of η Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

In the Poisson-Spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. The Poisson spot is the last of the classical optics experiments to be realized with neutral matter waves. In this paper we report the observation of Poisson's Spot using a beam of neutral deuterium molecules. The wavelength-independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large-molecule diffraction and coherence in atom-lasers to patterning with large molecules.

We report the detection toward {eta} Carinae of six new molecules, CO, CN, HCO{sup +}, HCN, HNC, and N{sub 2}H{sup +}, and of two of their less abundant isotopic counterparts, {sup 13}CO and H{sup 13}CN. The line profiles are moderately broad ({approx}100 km s{sup -1}), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO{sup +} do not appear to be underabundant in {eta} Carinae. On the other hand, molecules containing nitrogen or the {sup 13}C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of {eta} Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

This Account describes a new paradigm for the relationship between the geometry of metallic nanostructures and their optical properties. While the interaction of light with metallic nanoparticles is determined by their collective electronic or plasmon response, a compelling analogy exists between plasmon resonances of metallic nanoparticles and wave functions of simple atoms and molecules. Based on this insight, an entire family of plasmonic nanostructures, artificial molecules, has been developed whose optical properties can be understood within this picture: nanoparticles (nanoshells, nanoeggs, nanomatryushkas, nanorice), multi-nanoparticle assemblies (dimers, trimers, quadrumers), and a nanoparticle-over-metallic film, an electromagnetic analog of the spinless Anderson model. PMID:17226945

The feasibility of using data compression to improve link efficiency as an alternative to increased transmitter power, reducing receiver noise figures, increasing antenna gain through more stringent orbiter attitude constraints, etc. is studied. A method of encoding digital data is developed which permits low band-width encoding as well as a unique system of adaptive run length encoding. The effectiveness of these techniques for the air-to-ground link and for the bandwidth-limited ground-to-ground data link used for the orbiter downlink data is evaluated. Results are presented.

Proposed pulse vector-excitation speech encoder (PVXC) encodes analog speech signals into digital representation for transmission or storage at rates below 5 kilobits per second. Produces high quality of reconstructed speech, but with less computation than required by comparable speech-encoding systems. Has some characteristics of multipulse linear predictive coding (MPLPC) and of code-excited linear prediction (CELP). System uses mathematical model of vocal tract in conjunction with set of excitation vectors and perceptually-based error criterion to synthesize natural-sounding speech.

A programmable pulse-position-modulation (PPM) encoder has been designed for use in testing an optical communication link. The encoder includes a programmable state machine and an electronic code book that can be updated to accommodate different PPM coding schemes. The encoder includes a field-programmable gate array (FPGA) that is programmed to step through the stored state machine and code book and that drives a custom high-speed serializer circuit board that is capable of generating subnanosecond pulses. The stored state machine and code book can be updated by means of a simple text interface through the serial port of a personal computer.

This article presents a broad view of the need for regulatory guidance when confronting the problem of acid rain. The two major topics addressed are (1) Why is guidance needed and (2) What kind of guidance is needed. Discussion of rate and accounting treatment of allowances, acid rain compliance planning, and allowance trading and energy efficiency are included.

California State Dept. of Education, Sacramento. Bureau of Adult Education.

This guide provides an in-depth description of guidance and counseling as they relate to adult education. One major theme stressed is that guidance is an integral part of adult education, serving students by facilitating their learning and self-fulfillment. Topics covered are the concept of guidance within adult education and the adult education…

This book contains a collection of 14 papers dealing with guidance and guidance programs in the Philippines, the Republic of China, Japan, and Thailand. An overview of the place of American counselors in international guidance and benefits to counselors and the counseling profession of world-wide contacts is reviewed in the initial paper. Issues…

Elementary school teachers were trained in seven guidance learnings over a two-day span so that they could use guidance approaches in their classes. The Guidance Learning Rating Scale was developed to evaluate statements before and after their exposure to confluent education activities. There were significant changes in test scores in the expect…

This paper presents a guidance concept for use on the first stage of a Mars Ascent Vehicle (MAV). The guidance is based on a calculus of variations approach similar to that used for the final phase of the Apollo Earth return guidance. A three degree-of-freedom (3DOF) Monte Carlo simulation is used to evaluate performance and robustness of the algorithm.

The automatic guidance of rotorcraft for obstacle avoidance in nap-of-the-earth flight is studied. A hierarchical breakdown of the guidance components is used to identify the functional requirements. These requirements and anticipated sensor capabilities lead to a preliminary guidance concept, which has been evaluated via computer simulations.

This report reviews the structure of the guidance field and provides a sector-by-sector analysis of current quality assurance arrangements in the United Kingdom. Part 1 presents an outline of the guidance sector, including some key concepts, structures, and roles. It defines guidance and other terms; discusses the three main categories…

Problems faced by American Indian college students were described in these 2 guidance and counseling papers. The first paper suggested a plan for a guidance and counseling program. The 3 steps in this plan were a special summer student orientation program for Indians; and "out-reaching" guidance and counseling program where Indian students would…

The original G-Guidance algorithm provided an autonomous guidance and control policy for small-body proximity operations that took into account uncertainty and dynamics disturbances. However, there was a lack of robustness in regards to object proximity while in autonomous mode. The modified GGuidance algorithm was augmented with a second operational mode that allows switching into a safety hover mode. This will cause a spacecraft to hover in place until a mission-planning algorithm can compute a safe new trajectory. No state or control constraints are violated. When a new, feasible state trajectory is calculated, the spacecraft will return to standard mode and maneuver toward the target. The main goal of this augmentation is to protect the spacecraft in the event that a landing surface or obstacle is closer or further than anticipated. The algorithm can be used for the mitigation of any unexpected trajectory or state changes that occur during standard mode operations

The world of work as part of our dynamic society is the result of a permanent change. This development has an influence on the school and its tasks. Apart from industrialisation there is computerisation which requires, to an important extent, individual judgement and inventiveness on the part of the working population. The school has not only to cope with these changes but has also to try to influence them through vocational orientation and guidance and its continual reform. The aim of the school is the development of a critical sense with the purpose of humanising the whole process. The importance of vocational orientation and guidance is increasing, and they have to become a task of our schools. The topic should therefore also be included in teacher training as well as in further education.

We investigate the effects of nanotopographical surfaces on the cell migration and cell shape dynamics of the amoeba Dictyostelium discoideum. Amoeboid motion exhibits significant contact guidance along surfaces with nanoscale ridges or grooves. We show quantitatively that nanoridges spaced 1.5 μm apart exhibit the greatest contact guidance efficiency. Using principal component analysis, we characterize the dynamics of the cell shape modulated by the coupling between the cell membrane and ridges. We show that motion parallel to the ridges is enhanced, while the turning, at the largest spatial scales, is suppressed. Since protrusion dynamics are principally governed by actin dynamics, we imaged the actin polymerization of cells on ridges. We found that actin polymerization occurs preferentially along nanoridges in a ``monorail'' like fashion. The ridges then provide us with a tool to study actin dynamics in an effectively reduced dimensional system.

A taxonomy is an ordered classification system. In error reduction analysis, an examination of the human failures that lead to an event often uses a taxonomy to classify the failures according to some aspect of their characteristics. These classifications provide insights into the forces that kept the persons involved from achieving their intended actions. They also can provide guidance for changing the situation to prevent failure in the future. For example, the corrective action would be different if a therapist pressed the wrong button because several buttons looked alike or they forgot which button to press. Different types of failures lead to particular types of remediation. Taxonomies can provide guidance in selecting between possible corrective actions.

The adaptive potential of video guidance technology for earth orbital and interplanetary missions was explored. The application of video acquisition, pointing, tracking, and navigation technology was considered to three primary missions: planetary landing, earth resources satellite, and spacecraft rendezvous and docking. It was found that an imaging system can be mechanized to provide a spacecraft or satellite with a considerable amount of adaptability with respect to its environment. It also provides a level of autonomy essential to many future missions and enhances their data gathering ability. The feasibility of an autonomous video guidance system capable of observing a planetary surface during terminal descent and selecting the most acceptable landing site was successfully demonstrated in the laboratory. The techniques developed for acquisition, pointing, and tracking show promise for recognizing and tracking coastlines, rivers, and other constituents of interest. Routines were written and checked for rendezvous, docking, and station-keeping functions.

This article describes the basic principles of evaluation, focusing on the evaluation of healthcare services. It emphasises the importance of evaluation in the current healthcare environment and the requirement for nurses to understand the essential principles of evaluation. Evaluation is defined in contrast to audit and research, and the main theoretical approaches to evaluation are outlined, providing insights into the different types of evaluation that may be undertaken. The essential features of preparing for an evaluation are considered, and guidance provided on working ethically in the NHS. It is important to involve patients and the public in evaluation activity, offering essential guidance and principles of best practice. The authors discuss the main challenges of undertaking evaluations and offer recommendations to address these, drawing on their experience as evaluators. PMID:27380702

We propose a vibrotactile interface in the form of a belt for guiding blind walkers. This interface enables blind walkers to receive haptic directional instructions along complex paths without negatively impacting users' ability to listen and/or perceive the environment the way some auditory directional instructions do. The belt interface was evaluated in a controlled study with 10 blind individuals and compared to the audio guidance. The experiments were videotaped and the participants' behaviors and comments were content analyzed. Completion times and deviations from ideal paths were also collected and statistically analyzed. By triangulating the quantitative and qualitative data, we found that the belt resulted in closer path following to the expense of speed. In general, the participants were positive about the use of vibrotactile belt to provide directional guidance. PMID:25781953

Migration is an increasingly commonplace phenomenon for a number of reasons. People migrate from rural to urban areas or across borders for reasons including economic, educational or political. There is increasing recent research evidence from many countries in Europe that indicates that migrants are more prone to certain psychiatric disorders. Because of their experiences of migration and settling down in the new countries, they may also have special needs such as lack of linguistic abilities which must be taken into account using a number of strategies at individual, local and national policy levels. In this guidance document, we briefly present the evidence and propose that specific measures must be taken to improve and manage psychiatric disorders experienced by migrants and their descendants. This improvement requires involvement at the highest level in governments. This is a guidance document and not a systematic review. PMID:24503244

The Guidance for UMTRA Project Surveillance and Maintenance describes the procedures that will be used to verify that Uranium Mill Tailings Remedial Action (UMTRA) Project disposal sites continue to function as designed. The approach of this guidance document is to identify surveillance requirements and maintenance procedures that will be used to comply with NRC license requirements. This document addresses five primary activities: Definition and characterization of final site conditions. Site inspections; Ground-water monitoring; Aerial photography; and Custodial maintenance and contingency repair. Final site conditions will be defined and characterized prior to the completion of remedial actions at a site. As-built drawings will be compiled, a final topographic survey will be performed, a vicinity map will be prepared, and ground and aerial photographs will be taken. Survey monuments, site markers, and signs will be established as will a network of monitoring wells.

The Ballistic Missile Office (BMO) has developed and employed a procedure to insure the flight readiness of a Peacekeeper guidance system. The goals of this additional review procedure (over and above acceptance testing) are to minimize the risk of the guidance system failure and/or achieving substantially less than the designed accuracy. The roles, mission and interaction of teams of personnel from seven associate contractors are discussed using flow diagrams. The paper also includes methods used to identify and resolve areas of concern as well as examples of actual concerns discovered. The scope is discused, including both the various technical disciplines involved and the lowest level of build and test areas reviewed. Resulting build and test improvements are shown.

This paper argues that, contrary to a common line of criticism followed by scholars such as Helga Kuhse, a particularistic version of virtue ethics properly elaborated, can provide sound moral guidance and a satisfactory account for moral justification of our opinions regarding, for instance, health care practice. In the first part of the paper, three criteria for comparing normative theories with respect to action-guiding power are outlined, and it is argued that the presented particularistic version of virtue ethics actually can provide more guidance than the universalistic theories followed by Kuhse and others. In the second part of the paper it is claimed that universalist normative theories have serious problems accounting for the role that moral principles are supposed to play in the justification, of moral opinions, whereas the present version of virtue ethics accommodates a plausible alternative idea of justification without invoking moral principles or eschewing objectivity. PMID:11758585

The paper presents a robotic method of performing low dose rate prostate brachytherapy under magnetic resonance imaging (MRI) guidance. The design and operation of a fully automated MR compatible seed injector is presented. This is used with the MrBot robot for transperineal percutaneous prostate access. A new image-registration marker and algorithms are also presented. The system is integrated and tested with a 3T MRI scanner. Tests compare three different registration methods, assess the precision of performing automated seed deployment, and use the seeds to assess the accuracy of needle targeting under image guidance. Under the ideal conditions of the in vitro experiments, results show outstanding image-guided needle and seed placement accuracy. PMID:17694871

Certain environmental parameters are accessible to cells only indirectly and require an encoding step for cells to retrieve the relevant information. A prominent example is the phenomenon of quorum sensing by microorganisms, where information about cell density is encoded by means of secreted signaling molecules. The mapping of cell density to signal molecule concentration and the corresponding network modules involved have been at least partially characterized in many bacteria, and vary markedly between different systems. In this study, we investigate theoretically how differences in signal transport, signal modification, and site of signal detection shape the encoding function and affect the sensitivity and the noise characteristics of the cell-density-encoding process. We find that different modules are capable of implementing both fairly basic as well as more complex encoding schemes, whose qualitative characteristics vary with cell density and are linked to network architecture, providing the basis for a hierarchical classification scheme. We exploit the tight relationship between encoding behavior and network architecture to constrain the network topology of partially characterized natural systems, and verify one such prediction by showing experimentally that Vibrio harveyi is capable of importing Autoinducer 2. The framework developed in this research can serve not only to guide reverse engineering of natural systems but also to stimulate the design of synthetic systems and generally facilitate a better understanding of the complexities arising in the quorum-sensing process because of variations in the physical organization of the encoder network module. PMID:24988360

We studied the infrared image guidance for ground vehicle based on the fast wavelet image focusing and tracking. Here we uses the image of the uncooled infrared imager mounted on the two axis gimbal system and the developed new auto focusing algorithm on the Daubechies wavelet transform. The developed new focusing algorithm on the Daubechies wavelet transform processes the result of the high pass filter effect to meet the direct detection of the objects. This new focusing gives us the distance information of the outside world smoothly, and the information of the gimbal system gives us the direction of objects in the outside world to match the sense of the spherical coordinate system. We installed this system on the hand made electric ground vehicle platform powered by 24VDC battery. The electric vehicle equips the rotary encoder units and the inertia rate sensor units to make the correct navigation process. The image tracking also uses the developed newt wavelet focusing within several image processing. The size of the hand made electric ground vehicle platform is about 1m long, 0.75m wide, 1m high, and 50kg weight. We tested the infrared image guidance for ground vehicle based on the new wavelet image focusing and tracking using the electric vehicle indoor and outdoor. The test shows the good results by the developed infrared image guidance for ground vehicle based on the new wavelet image focusing and tracking.

This article summarizes the highlights of recent events and developments in guidance, navigation, and control in space, aircraft, and weapons. This article is about 1,200 words long. Information for the article was collected from other NASA Centers, DoD, and industry. All information was previously cleared by the originating organizations. Information for the article was also gathered from Aviation Week and Space Technology, Space News, and similar sources.

Various methods can be used to decontaminate breast pump milk collection kits and items related to infant feeding but they have some drawbacks and risks. In 2015, the Joint Working Group of the Healthcare Infection Society and Infection Prevention Society published guidance to support the safe decontamination of this equipment at home and in hospital. This article summarises its recommendations for health professionals to use and communicate to other groups, such as parents and carers. PMID:27400623

This article summarizes the highlights of recent events and developments in guidance, navigation, and control in space, aircraft, and weapons. This article is about 1,200 words long. Information for the article was collected from other NASA centers, DoD, and industry. All information was previously cleared by the originating organizations. Information for the article was also gathered from Aviation Week and Space Technology, Space News, and similar sources.

The role of economic evaluation in the efficient allocation of healthcare resources has been widely debated. Whilst economic evidence is undoubtedly useful to purchasers, it does not address the issue of affordability which is an increasing concern. Healthcare purchasers are concerned not just with maximising efficiency but also with the more simplistic goal of remaining within their annual budgets. These two objectives are not necessarily consistent. This paper examines the issue of affordability, the relationship between affordability and efficiency and builds the case for why there is a growing need for budget impact models to complement economic evaluation. Guidance currently available for such models is also examined and it is concluded that this guidance is currently insufficient. Some of these insufficiencies are addressed and some thoughts on what constitutes best practice in budget impact modelling are suggested. These suggestions include consideration of transparency, clarity of perspective, reliability of data sources, the relationship between intermediate and final end-points and rates of adoption of new therapies. They also include the impact of intervention by population subgroups or indications, reporting of results, probability of re-deploying resources, the time horizon, exploring uncertainty and sensitivity analysis, and decision-maker access to the model. Due to the nature of budget impact models, the paper does not deliver stringent methodological guidance on modelling. The intention was to provide some suggestions of best practice in addition to some foundations upon which future research can build. PMID:11456210

The terminal guidance system (TGS) is avionic equipment which gives guidance along a curved descending flight path to a landing. A Cessna 182 was used as the test aircraft and the TGS was installed and connected to the altimeter, DME, RMI, and gyro compass. Approaches were flown by three different pilots. When the aircraft arrives at the termination point, it is set up on final approach for a landing. The TGS provides guidance for curved descending approaches with guideslopes of 6 deg which required, for experienced pilots, workloads that are approximately the same as for an ILS. The glideslope is difficult to track within 1/2 n.m. of the VOR/DME station. The system permits, for experienced pilots, satisfactory approaches with a turn radius as low as 1/2 n.m. and a glideslope of 6 deg. Turn angles have little relation to pilot workload for curved approaches. Pilot experience is a factor for curved approaches. Pilots with low instrument time have difficulty flying steep approaches with small turn radius. Turbulence increases the pilot workload for curved approaches. The TGS does not correct to a given flight path over the ground nor does it adequately compensate for wind drift.

Embedded software has been developed specifically for controlling an Advanced Video Guidance Sensor (AVGS). A Video Guidance Sensor is an optoelectronic system that provides guidance for automated docking of two vehicles. Such a system includes pulsed laser diodes and a video camera, the output of which is digitized. From the positions of digitized target images and known geometric relationships, the relative position and orientation of the vehicles are computed. The present software consists of two subprograms running in two processors that are parts of the AVGS. The subprogram in the first processor receives commands from an external source, checks the commands for correctness, performs commanded non-image-data-processing control functions, and sends image data processing parts of commands to the second processor. The subprogram in the second processor processes image data as commanded. Upon power-up, the software performs basic tests of functionality, then effects a transition to a standby mode. When a command is received, the software goes into one of several operational modes (e.g. acquisition or tracking). The software then returns, to the external source, the data appropriate to the command.

A performance evaluation of the Hybrid Predictor corrector Aerocapture Scheme (HYPAS) guidance algorithm for aerocapture at Neptune is presented in this paper for a Mission to Neptune and the Neptune moon Triton'. This mission has several challenges not experienced in previous aerocapture guidance assessments. These challengers are a very high Neptune arrival speed, atmospheric exit into a high energy orbit about Neptune, and a very high ballistic coefficient that results in a low altitude acceleration capability when combined with the aeroshell LD. The evaluation includes a definition of the entry corridor, a comparison to the theoretical optimum performance, and guidance responses to variations in atmospheric density, aerodynamic coefficients and flight path angle for various vehicle configurations (ballistic numbers). The benefits of utilizing angle-of-attack modulation in addition to bank angle modulation to improve flight performance is also discussed. The results show that despite large sensitivities in apoapsis targeting, the algorithm performs within the allocated AV budget for the Neptune mission bank angle only modulation. The addition of angle-of-attack modulation with as little as 5 degrees of amplitude significantly improves the scatter in final orbit apoapsis. Although the angle-of-attack modulation complicates the vehicle design, the performance enhancement reduces aerocapture risk and reduces the propellant consumption needed to reach the high energy target orbit for a conventional propulsion system.

The stress of migration as well as social factors and changes related to the receiving society may lead to the manifestation of psychiatric disorders in vulnerable individuals after migration. The diversity of cultures, ethnicities, races and reasons for migration poses a challenge for those seeking to understand how illness is experienced by immigrants whose backgrounds differ significantly from their clinicians. Cultural competence represents good clinical practice and can be defined as such that a clinician regards each patient in the context of the patient's own culture as well as from the perspective of the clinician's cultural values and prejudices. The EPA Guidance on cultural competence training outlines some of the key issues related to cultural competence and how to deal with these. It points out that cultural competence represents a comprehensive response to the mental health care needs of immigrant patients and requires knowledge, skills and attitudes which can improve the effectiveness of psychiatric treatment. To reach these aims, both individual and organizational competence are needed, as well as teaching competence in terms of educational leadership. The WPA Guidance on Mental Health and Mental Health Care for Migrants and the EPA Guidance on Mental Health Care for Migrants list a series of recommendations for policy makers, service providers and clinicians; these are aimed at improving mental health care for immigrants. The authors of this paper would like to underline these recommendations and, focusing on cultural competency and training, believe that they will be of positive value. PMID:25725596

The Apollo guidance computer was designed to provide the computation necessary for guidance, navigation and control of the command module and the lunar landing module of the Apollo spacecraft. The computer was designed using the technology of the early 1960's and the production was completed by 1969. During the development, production, and operational phase of the program, the computer has accumulated a very interesting history which is valuable for evaluating the technology, production methods, system integration, and the reliability of the hardware. The operational experience in the Apollo guidance systems includes 17 computers which flew missions and another 26 flight type computers which are still in various phases of prelaunch activity including storage, system checkout, prelaunch spacecraft checkout, etc. These computers were manufactured and maintained under very strict quality control procedures with requirements for reporting and analyzing all indications of failure. Probably no other computer or electronic equipment with equivalent complexity has been as well documented and monitored. Since it has demonstrated a unique reliability history, it is important to evaluate the techniques and methods which have contributed to the high reliability of this computer.

The United States Army is currently looking for new methods of guiding munitions, which would allow the military to employ guided munitions in place of traditional munitions. This will give the US Army an edge on the battle field and also allow the use of munitions in areas where traditional mortars and artillery cannot be used, including dense urban environments where collateral damage is not acceptable. In this thesis, an innovative approach to Guidance, Navigation, and Control (GN&C) is developed for a spinning projectile that utilizes a single axis canard actuation system. Utilizing the projectiles spin, the controller can provide a full range of aerodynamic forces, over the 360° of rotation, that provides maneuverability using only one actuator. This technique minimizes the need for multiple actuators and maintains the inherent aerodynamic stability provided by the spin. The GN&C system design described in this thesis consists of a tracking regulator for sinusoidally oscillating the canard system, a nonlinear state estimator for attitude measurement, and a guidance law to guide the projectile to a target. By combining the three components, we can demonstrate a closed-loop guidance system that will hit a target accurately at distances normally not achieved by an unguided projectile.

The in-cockpit swath centerline identifier (SCI) for aerial applicators uses differentially corrected global positioning system (GPS) signals to determine precise ground track of an aircraft and provide guidance to the pilot for flying patterns for aerial application of materials such as pesticides, herbicides, and fertilizers. Cross track distance from the swath centerline is provided by a heads up light bar display while detailed navigation, position, and status information is provided on an alphanumeric display on a panel mounted console. This system provides straight line guidance when executing a swath and turn-in guidance when proceeding from one swath to the next. It provides a record of the swaths which were sprayed and logs all of the associated navigation and operational data, including time. In addition, it provides navigation information from base to the fields, between fields, and return. The SCI eliminates the need for flaggers while providing improved accuracy of application. Reduced exposure to liability and improved quality control results as the position, altitude, time, and spray status are logged for post flight analysis. The SCI has been used in commercial agricultural applications. Demonstrations of the SCI showed better precision than anticipated.

Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

An algebraic formulation of quantum mechanics is presented. In this formulation, operators of interest are expanded onto elements of an algebra, G. For bound state problems in nu dimensions the algebra G is taken to be U(nu + 1). Applications to the structure of molecules are presented.

As part of the SMATHematics Project: The Wonder of Science, The Power of Mathematics--a collaborative partnership between Kennesaw State University and two local school districts, fifth graders had the opportunity to puzzle out chemical formulas of propane, methanol, and other important molecules. In addition, they explored properties that…

One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

The author maintains that chemistry has a key role as the science of molecules and rejects the concept of chemistry as a branch of physics. The scope of chemistry, the philosophies underlying its practice, and the teaching of the subject also are discussed. (DT)

The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

We analyzed the direct sampling (DS) method for diffractive lens encoding, using exact electromagnetic diffraction theory. In addition to previously published research [Pure Appl. Opt. 7, 565 (1998)] we present what we believe to be new results for TM polarization. We found that the validity of the scalar-based DS method is even more extended for TM than for TE polarization. Additionally, we fabricated and characterized DS-encoded blazed gratings and found good agreement between the experimental and theoretical diffraction efficiencies. We analyzed quantitatively the influence of the encoding schemes DS and analytic quantization (AQ) on the quality of the focal spot. We also investigated the focal spot sizes (FWHM) and the Strehl ratios of the DS- and the AQ-encoded cylindrical lenses. PMID:18354523

The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

The present invention relates to variants of a parent cellobiohydrolase. The present invention also relates to polynucleotides encoding the cellobiohydrolase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the cellobiohydrolase variants.

Nucleotide sequences, derived from a thermophilic actinomycete microorganism, which encode a thermostable alkaline protease are disclosed. Also disclosed are variants of the nucleotide sequences which encode a polypeptide having thermostable alkaline proteolytic activity. Recombinant thermostable alkaline protease or recombinant polypeptide may be obtained by culturing in a medium a host cell genetically engineered to contain and express a nucleotide sequence according to the present invention, and recovering the recombinant thermostable alkaline protease or recombinant polypeptide from the culture medium.

Nucleotide sequences, derived from a thermophilic actinomycete microorganism, which encode a thermostable alkaline protease are disclosed. Also disclosed are variants of the nucleotide sequences which encode a polypeptide having thermostable alkaline proteolytic activity. Recombinant thermostable alkaline protease or recombinant polypeptide may be obtained by culturing in a medium a host cell genetically engineered to contain and express a nucleotide sequence according to the present invention, and recovering the recombinant thermostable alkaline protease or recombinant polypeptide from the culture medium. 3 figs.

We demonstrate the spreading of femtosecond optical pulses into picosecond-duration pseudonoise bursts. Spreading is accomplished by encoding pseudorandom binary phase codes onto the optical frequency spectrum. Subsequent decoding of the spectral phases restores the original pulse. We propose that frequency-domain encoding and decoding of coherent ultrashort pulses could form the basis for a rapidly reconfigurable, code-division multiple-access optical telecommunications network. PMID:19745879

modENCODE was a 5 yr NHGRI funded project (2007– 2012) to map the function of every base in the genomes of worms and flies characterizing positions of modified histones and other chromatin marks, origins of DNA replication, RNA transcripts and the transcription factor binding sites that control gene expression. Here we describe the Drosophila modENCODE datasets and how best to access and use them for genome wide and individual gene studies. PMID:24636835

Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

This paper explores the essential understanding and underlying perspectives of career implicit in EU career guidance policy in the twenty-first century, as well as the possible implications of these for the future mission of guidance. Career theories, models and concepts that serve career guidance are shaped on the twentieth-century industrial…

..., and ease of reading. The draft of this guidance issued on September 28, 2010 (75 FR 59726) and the... supersedes the guidance with the same name that issued on April 3, 2007 (72 FR 15888). II. Significance of...; Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological...

... of May 2, 2006 (71 FR 25844), we announced the availability of a guidance entitled ``Guidance on the... Cosmetic Act; Withdrawal of Guidance AGENCY: Food and Drug Administration, HHS. ACTION: Notice; withdrawal... 403(w) of the Federal Food, Drug, and Cosmetic Act,'' dated April 2006, that was announced in...

...The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials.'' This guidance summarizes FDA's current thoughts on the appropriate use of Bayesian statistical methods in the design and analysis of medical device clinical...

Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal’s ability to locate the source of odor cues in realistic turbulent environments—a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing. PMID:26730727

Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal's ability to locate the source of odor cues in realistic turbulent environments-a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing. PMID:26730727

Receptors on the growth cone at the leading edge of elongating axons play critical guidance roles by recognizing cues via their extracellular domains and transducing signals via their intracellular domains, resulting in changes in direction of growth. An important concept to have emerged in the axon guidance field is the importance of repulsion as a major guidance mechanism. Given the number and variety of different repulsive receptors, it is generally thought that there are likely to be qualitative differences in the signals they transduce. However, the nature of these possible differences is unknown. By creating chimeras using the extracellular and intracellular domains of three different Drosophila repulsive receptors, Unc5, Roundabout (Robo), and Derailed (Drl) and expressing them in defined cells within the embryonic nervous system, we examined the responses elicited by their intracellular domains systematically. Surprisingly, we found no qualitative differences in growth cone response or axon growth, suggesting that, despite their highly diverged sequences, each intracellular domain elicits repulsion via a common pathway. In terms of the signaling pathway(s) used by the repulsive receptors, mutations in the guanine nucleotide exchange factor Trio strongly enhance the repulsive activity of all three intracellular domains, suggesting that repulsion by Unc5, Robo, and Drl, and perhaps repulsion in general, involves Trio activity. SIGNIFICANCE STATEMENT A prevailing concept that has emerged in the axon guidance field is the importance of repulsion as a guidance mechanism for steering axons to their appropriate targets. Given the number and variety of different repulsive receptors, it is generally thought that there are differences in the signals that they transduce. However, this has never been tested directly. We have used the advanced genetics of Drosophila to compare directly the outputs of different repulsive receptors. Surprisingly, we found no qualitative

The space vehicle guidance problem is formulated using a neural network approach, and the appropriate neural net architecture for modeling optimum guidance trajectories is investigated. In particular, an investigation is made of the incorporation of prior knowledge about the characteristics of the optimal guidance solution into the neural network architecture. The online classification performance of the developed network is demonstrated using a synthesized network trained with a database of optimum guidance trajectories. Such a neural-network-based guidance approach can readily adapt to environment uncertainties such as those encountered by an AOTV during atmospheric maneuvers.

In this paper, the problem of 3-dimensional guidance law design is considered and a new guidance law based on partial sliding mode technique is presented. The approach is based on the classification of the state variables within the guidance system dynamics with respect to their required stabilization properties. In the proposed law by using a partial sliding mode technique, only trajectories of a part of states variables are forced to reach the partial sliding surfaces and slide on them. The resulting guidance law enables the missile to intercept highly maneuvering targets within a finite interception time. Effectiveness of the proposed guidance law is demonstrated through analysis and simulations. PMID:23260528

Axon guidance is a crucial part of neural circuit formation. While precise axonal targeting forms the basis of accurate information delivery, the mechanisms that regulate this process are still unclear. Apoptotic signaling molecules have been identified in the axon terminal, but their specific role in axon guidance is not well understood. Here we use the mouse olfactory system as an in vivo model to demonstrate that by modulating Fas-associated factor 1 (FAF1), an apoptosis regulatory molecule, we can rewire axonal projections. Interestingly, FAF1 is highly expressed in the developing mouse olfactory system, but its expression is downregulated postnatally. Using a tetracycline-inducible promoter Tet-Off system, we generated transgenic mice in which FAF1 is specifically expressed in immature olfactory sensory neurons (OSNs) and show that overexpression of FAF1 not only misroutes OSN axons to deep layers of the olfactory bulb but also leads to widespread disruption of the glomerular layer. In addition, we also demonstrate that the specific convergence of P2 receptor OSN axons is completely distorted in the FAF1 mice. Strikingly, all of the mutant phenotypes can be recovered by shutting down FAF1 expression through the administration of doxycycline. Together, our study provides clear in vivo evidence that an apoptotic molecule can indeed regulate axon targeting and that OSNs can restore their organization even after broad disruption. PMID:21849551

Combinatorial expression of transcription factors forms transcriptional codes to confer neuronal identities and connectivity. However, how these intrinsic factors orchestrate the spatiotemporal expression of guidancemolecules to dictate the responsiveness of axons to guidance cues is less understood. Thalamocortical axons (TCAs) represent the major input to the neocortex and modulate cognitive functions, consciousness and alertness. TCAs travel a long distance and make multiple target choices en route to the cortex. The homeodomain transcription factor Gbx2 is essential for TCA development, as loss of Gbx2 abolishes TCAs in mice. Using a novel TCA-specific reporter, we have discovered that thalamic axons are mostly misrouted to the ventral midbrain and dorsal midline of the diencephalon in Gbx2-deficient mice. Furthermore, conditionally deleting Gbx2 at different embryonic stages has revealed a sustained role of Gbx2 in regulating TCA navigation and targeting. Using explant culture and mosaic analyses, we demonstrate that Gbx2 controls the intrinsic responsiveness of TCAs to guidance cues. The guidance defects of Gbx2-deficient TCAs are associated with abnormal expression of guidance receptors Robo1 and Robo2. Finally, we demonstrate that Gbx2 controls Robo expression by regulating LIM-domain transcription factors through three different mechanisms: Gbx2 and Lhx2 compete for binding to the Lmo3 promoter and exert opposing effects on its transcription; repressing Lmo3 by Gbx2 is essential for Lhx2 activity to induce Robo2; and Gbx2 represses Lhx9 transcription, which in turn induces Robo1. Our findings illustrate the transcriptional control of differential expression of Robo1 and Robo2, which may play an important role in establishing the topography of TCAs. PMID:23136391

We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the point of

Molecular biology, genomics and proteomics methods have been utilized to reveal a non-annotated class of endogenous polypeptides (small proteins and peptides) encoded by short open reading frames (sORFs), or small open reading frames (smORFs). We refer to these polypeptides as s(m)ORF-encoded polypeptides or SEPs. The early SEPs were identified via genetic screens, and many of the RNAs that contain s(m)ORFs were originally considered to be non-coding; however, elegant work in bacteria and flies demonstrated that these s(m)ORFs code for functional polypeptides as small as 11-amino acids in length. The discovery of these initial SEPs led to search for these molecules using methods such as ribosome profiling and proteomics, which have revealed the existence of many SEPs, including novel human SEPs. Unlike screens, omics methods do not necessarily link a SEP to a cellular or biological function, but functional genomic and proteomic strategies have demonstrated that at least some of these newly discovered SEPs have biochemical and cellular functions. Here, we provide an overview of these results and discuss the future directions in this emerging field. PMID:25857697

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase. PMID:26061191

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.

Midcourse guidance is commonly designed to save as much energy as possible so that the missile's final speed can be maximized while entering the homing stage. For this purpose, a competitive guidance design should be able to generate an admissible flight trajectory as to bring the interceptor to a superior altitude for a favorable target engagement. In this paper, a new adaptive trajectory shaping guidance scheme based on the adaptive fuzzy inference system, which is capable of generating a variety of trajectories for efficient target interception, is presented. The guidance law is developed with the aim of saving the interceptor's energy conservation while improving performance robustness. Applications of the presented approach have included a variety of mission oriented guidance, such as cruise missile guidance, anti-ballistic missile guidance, etc. PMID:19054508

This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed. PMID:17038427

A novel method for the detection and identification of single molecules in solution has been devised, computer simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required for individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed before-hand in order to estimate the experimental feasibility of the method and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented. 20 refs., 8 figs.

The formation of functional connectivity in the nervous system is governed by axon guidance that instructs nerve growth and branching during development, implying a similarity between neuronal subtypes in terms of nerve extension. We demonstrate the molecular mechanism of another layer of complexity in vertebrates by defining a transcriptional program underlying growth differences between positionally different neurons. The rate of axon extension of the early subset of embryonic dorsal root ganglion sensory neurons is encoded in neurons at different axial levels. This code is determined by a segmental pattern of axial levels of Runx family transcription factor Runx3. Runx3 in turn determines transcription levels of genes encoding cytoskeletal proteins involved in axon extension, including Rock1 and Rock2 which have ongoing activities determining axon growth in early sensory neurons and blocking Rock activity reverses axon extension deficits of Runx3−/− neurons. Thus, Runx3 acts to regulate positional differences in axon extension properties apparently without affecting nerve guidance and branching, a principle that could be relevant to other parts of the nervous system. PMID:22903063

Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

The incoherence between measurement and sparsifying transform matrices and the restricted isometry property (RIP) of measurement matrix are two of the key factors in determining the performance of compressive sensing (CS). In CS-MRI, the randomly under-sampled Fourier matrix is used as the measurement matrix and the wavelet transform is usually used as sparsifying transform matrix. However, the incoherence between the randomly under-sampled Fourier matrix and the wavelet matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the mathematical result that noiselets are maximally incoherent with wavelets, this paper introduces the noiselet unitary bases as the measurement matrix to improve the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that compares the multichannel noiselet and multichannel Fourier measurement matrices in CS-MRI, we propose a multichannel compressive sensing (MCS) framework to take the advantage of multichannel data acquisition used in MRI scanners. Simulations are presented in the MCS framework to compare the performance of noiselet encoding reconstructions and Fourier encoding reconstructions at different acceleration factors. The comparisons indicate that multichannel noiselet measurement matrix has better RIP than that of its Fourier counterpart, and that noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image resolution and can achieve higher acceleration factors. To demonstrate the feasibility of the proposed noiselet encoding scheme, a pulse sequences with tailored spatially selective RF excitation pulses was designed and implemented on a 3T scanner to acquire the data in the noiselet domain from a phantom and a human brain. The results indicate that noislet encoding preserves image resolution better than Fouirer encoding. PMID:25965548

Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

Asphalthenes are typically defined as the fraction of petroleum insoluble in n-alkanes (typically heptane, but also hexane or pentane) but soluble in toluene. This fraction causes problems of emulsion formation and deposition/precipitation during crude oil production, processing and transport. From the definition it follows that asphaltenes are not a homogeneous fraction but is composed of molecules polydisperse in molecular weight, structure and functionalities. Their complexity makes the understanding of their properties difficult. Proper model molecules with well-defined structures which can resemble the properties of real asphaltenes can help to improve this understanding. Over the last ten years different research groups have proposed different asphaltene model molecules and studied them to determine how well they can mimic the properties of asphaltenes and determine the mechanisms behind the properties of asphaltenes. This article reviews the properties of the different classes of model compounds proposed and present their properties by comparison with fractionated asphaltenes. After presenting the interest of developing model asphaltenes, the composition and properties of asphaltenes are presented, followed by the presentation of approaches and accomplishments of different schools working on asphaltene model compounds. The presentation of bulk and interfacial properties of perylene-based model asphaltene compounds developed by Sjöblom et al. is the subject of the next part. Finally the emulsion-stabilization properties of fractionated asphaltenes and model asphaltene compounds is presented and discussed. PMID:25638443

Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

The physical conditions and chemical compositions of the gas in interstellar clouds are reviewed in light of the importance of interstellar clouds for star formation and the origin of life. The Orion A region is discussed as an example of a giant molecular cloud where massive stars are being formed, and it is pointed out that conditions in the core of the cloud, with a kinetic temperature of about 75 K and a density of 100,000-1,000,000 molecules/cu cm, may support gas phase ion-molecule chemistry. The Taurus Molecular Clouds are then considered as examples of cold, dark, relatively dense interstellar clouds which may be the birthplaces of solar-type stars and which have been found to contain the heaviest interstellar molecules yet discovered. The molecular species identified in each of these regions are tabulated, including such building blocks of biological monomers as H2O, NH3, H2CO, CO, H2S, CH3CN and H2, and more complex species such as HCOOCH3 and CH3CH2CN.

The epithelial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of ∼40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma, inflammatory pathophysiology, and tissue development and regeneration as well as its role in normal epithelial homeostasis. PMID:17600130

The Video Guidance Sensor (VGS) system is an optoelectronic sensor that provides automated guidance between two vehicles. In the original intended application, the two vehicles would be spacecraft docking together, but the basic principles of design and operation of the sensor are applicable to aircraft, robots, vehicles, or other objects that may be required to be aligned for docking, assembly, resupply, or precise separation. The system includes a sensor head containing a monochrome charge-coupled- device video camera and pulsed laser diodes mounted on the tracking vehicle, and passive reflective targets on the tracked vehicle. The lasers illuminate the targets, and the resulting video images of the targets are digitized. Then, from the positions of the digitized target images and known geometric relationships among the targets, the relative position and orientation of the vehicles are computed. As described thus far, the VGS system is based on the same principles as those of the system described in "Improved Video Sensor System for Guidance in Docking" (MFS-31150), NASA Tech Briefs, Vol. 21, No. 4 (April 1997), page 9a. However, the two systems differ in the details of design and operation. The VGS system is designed to operate with the target completely visible within a relative-azimuth range of +/-10.5deg and a relative-elevation range of +/-8deg. The VGS acquires and tracks the target within that field of view at any distance from 1.0 to 110 m and at any relative roll, pitch, and/or yaw angle within +/-10deg. The VGS produces sets of distance and relative-orientation data at a repetition rate of 5 Hz. The software of this system also accommodates the simultaneous operation of two sensors for redundancy

Magnetic resonance imaging typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here we propose the multi-dimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel RF coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. PMID:22926830

Configuration management (CM) is essential to maintaining an acceptable level of risk to the public, workers, environment, or mission success. It is a set of activities and techniques used to maintain consistency among physical and functional configuration, applicable requirements, and key documents. This document provides guidance for continuing the implementation of CM in a phased and graded manner. It describes a cost-effective approach to documented consistency with requirements, with early emphasis on items most important to safety and environmental protection. It is intended to help responsible line managers and configuration management staff personnel in meeting the Energy Systems configuration management policy standard.

This document provides guidance on Value Engineering (VE). VE is an organized team effort led by a person trained in the methodology to analyze the functions of projects, systems, equipment, facilities, services, and processes for achieving the essential functions at the lowest life cycle cost while maintaining required performance, reliability, availability, quality, and safety. VE has proven to be a superior tool to improve up-front project planning, cut costs, and create a better value for each dollar spent. This document forms the basis for the Environmental Restoration VE Program, describes the VE process, and provides recommendations on when it can be most useful on ER projects.